Molecular Genetic Nomenclature

Question 1

Which one of the following nomenclatures may be used to describe a functional, effective variant for MERRF?
A.c.8344A>G
B.g.8344A>G
C.m.8344A>G
D.n.8344A>G
E.r.8344A>G
F.p.8344A>G
G.None of the above

Answer 1

C.m.8344A>G

Question 2

Sanger sequencing of the TAZ gene on Xq28 for Barth syndrome was ordered. A C-to-G transversion in exon 5 was detected in John’s peripheral-blood sample, which was a nonsense mutation. Which one of the following nomenclatures may be used to describe this functional, effective variant?
A.c.153C>G
B.g.153C>G
C.m.153C>G
D.n.153C>G
E.r.153C>G
F.p.153C>G
G.None of the above

Answer 2

A.c.153C>G

Question 3

By sequencing only the exons and 20-bp introns on either side of the exons, one variant of unknown clinical significance (VUCS) was found, which changed an aspartic acid (Asp/D) into tyrosine (Tyr/Y). Which one of the nomenclatures may Dr. Z use to describe this variant at the DNA level?
A.a.1268C>T
B.c.1268C>T
C.g.1268C>T
D.p.1268C>T
E.All of the above
F.None of the above

Answer 3

B.c.1268C>T

Question 4

By sequencing only the exons and 20-bp introns on either side of the exons, one variant of unknown clinical significance (VUCS) was found, which changed an aspartic acid (Asp/D) into tyrosine (Tyr/Y). Which one of the nomenclatures may Dr. Z use to describe this variant at the amino acid level?
A.a.D401Y
B.c.D401Y
C.g.D401Y
D.p.D401Y
E.All of the above
F.None of the above

Answer 4

D.p.D401Y

Question 5

Which one of the following nomenclatures should be used to describe ACTTTGT[G]CC to ACTTTGT[GG]CC?
A.c.8dupG
B.c.8Gdup
C.c.8_9insG
D.c.8_9Gins
E.None of the above

Answer 5

A.c.8dupG

Question 6

If an individual has a maternally inherited c.35delG in GJB2 and a paternally inherited c.14C>T in GJB6, which one of the following nomenclatures would be appropriate to use in the molecular report?
A.GJB2:c.35delG;GJB6:c.14C>T
B.GJB2:c.[35delG];GJB6:c.[14C>T] C.GJB6:c.14C>T;GJB2:c.35delG
D.GJB6:c.[14C>T];GJB2:c.[35delG]
E.A and C
F.B and D
G.None of the above

Answer 6

F.B and D

Question 6

Which one of the following nomenclatures is appropriate, according to HGVS?
A.c.IVS2+2T>G
B.LRG_1:g.8463-2G>C
C.c.88+2U>G
D.c.*46T>A
E.All of the above
F.None of the above

Answer 6

D.c.*46T>A

Question 7

Which one of the following nomenclatures may be used to describe a start codon, methionine (Met, M), is changed to valine (Val, V), which activates an upstream translation initiation site at position –12?
A.p.-12Met
B.p.-12Met1
C.p.-12Met1Val
D.p.Met1Valext-12
E.None of the above

Answer 7

D.p.Met1Valext-12

Question 8

Which one of the following nomenclatures may be used to describe a variant in the stop codon at position 110 of an amino acid sequence, changing it to a codon for glutamine (Gln, Q) and adding a tail of 17 new amino acids (including Gln/Q) to the protein’s C-terminus ending at a new stop codon?
A.p.110Glnext17
B.p.Ter110Glnext17
C.p.Ter110Gln
D.p.110GlnextTer17
E.p.*110Gln

Answer 8

A.p.110Glnext17

Question 9

Which one of the following nomenclatures may be used to describe a chimeric organism in which a chromosome in some cells contains a normal sequence (arginine, Arg/R) at position 83, while other cells contain another chromosome with serine (Ser/S) at this position?
A.p.[Arg83=/Arg83Ser]
B.p.[Arg83=//Arg83Ser]
C.p.[Arg83=];[Arg83Ser]
D.p.[Arg83=;Arg83Ser]
E.p.[Arg83=(;)Arg83Ser]
F.None of the above

Answer 9

B.p.[Arg83=//Arg83Ser]

chimerism is described using “//.”
Mosaicism is described using “/.”

Question 10

Which one of the following nomenclatures may be used to describe a somatic mosaic case in which a chromosome in some cells contains a normal sequence (arginine, Arg/R) at position 83, while other cells contain a serine (Ser/S) at this position?
A.p.[Arg83=/Arg83Ser]
B.p.[Arg83=//Arg83Ser]
C.p.[Arg83=];[Arg83Ser]
D.p.[Arg83=;Arg83Ser]
E.p.[Arg83=(;)Arg83Ser]
F.None of the above

Answer 10

A.p.[Arg83=/Arg83Ser]

Question 11

Which one of the following nomenclatures may be used to describe two changes (amino acid alanine changes threonine at the position 25 and proline to leucine at the position 323, RNA or protein analyzed) were identified in one individual, but it is not known whether these changes are on the same chromosome (in cis) or on different chromosomes (in trans)?
A.p.[Arg83=/Arg83Ser]
B.p.[Arg83=//Arg83Ser]
C.p.[Arg83=];[Arg83Ser]
D.p.[Arg83=;Arg83Ser]
E.p.[Arg83=(;)Arg83Ser]
F.None of the above

Answer 11

E.p.[Arg83=(;)Arg83Ser]

two sequence changes in one gene with chromosomes unknown are described as “[change 1(;)change 2].” For example, p.[Ala25Thr(;)Pro323Leu] describes that two changes were identified in one individual (amino acid alanine-25 to threonine and proline-323 to leucine, RNA or protein analyzed), but it is not known whether these changes are on the same chromosome (in cis) or on different chromosomes (in trans).

p.[Ala25Thr];[Gly28Val] describes two changes derived from a gene on each chromosome (one paternal, one maternal);

If two independent changes in one individual are derived from one chromosome, they are described as “[first change;second change].” For example, p.[(Ala25Thr; Gly28Val)]

Question 12

Which one of the following nomenclatures may be used to describe a homozygous A-to-C change at the nucleotide position 76 of a cDNA?
A.c.[76A>C];[76A>C]
B.c.[76A>C];[(76A>C)]
C.c.[76A>C];[=]
D.c.[76A>C];[0]
E.None of the above

Answer 12

A.c.[76A>C];[76A>C]

Question 13

Which one of the following nomenclatures may be used to describe a heterozygous A-to-C change at the nucleotide position 76 of a cDNA?
A.c.[76A>C];[76A>C]
B.c.[76A>C];[(76A>C)]
C.c.[76A>C];[=]
D.c.[76A>C];[0]
E.None of the above

Answer 13

D.c.[76A>C];[0]

Question 14

Which one of the following nomenclatures may be used to describe a CHIMERIC case in which at position 83, in addition to the normal sequence (a G), some cells are found containing another chromosome containing a C at this position?
A.c.[83G=/83G>C]
B.c.[=/83G>C]
C.c.[83G=//83G>C]
D.c.[=//83G>C]
E.None of the above

Answer 14

D.c.[=//83G>C]

Question 15

Which one of the following nomenclatures may be used to describe a MOSAIC case in which at position 83, in addition to the normal sequence (a G), chromosomes are also found containing a C?
A.c.[83G=/83G>C]
B.c.[=/83G>C]
C.c.[83G=//83G>C]
D.c.[=//83G>C]
E.None of the above

Answer 15

A.c.[83G=/83G>C]

Question 16

Which one of the following nomenclatures is appropriate according to HGVS?
A.m.[76u>c]
B.m.[=,73_88del]
C.r.[76t>c]
D.r.[=,73_88del]
E.None of the above

Answer 16

C.r.[76t>c]

Mitochondrial DNAs are circulating DNAs in mitochondria, which are not diploid and do not contain U. So m.[=,73_88del] and m.[76u>c] are not correct.

Question 17

Which one of the following nomenclatures is appropriate, according to recommendations for the description of RNA sequence variants published by the HGVS?
A.r.[88G>A]
B.r.[=,73_88del]
C.r.[76T>C]
D.r.[76t>c,73_88del]
E.None of the above

Answer 17

B.r.[=,73_88del]

“r.” is used to indicate that a change is described at the RNA level, and nucleotides are designated by the bases (in lower case).

Question 18

A reference sequence in the table below is mutated to … cag ATG [T]CC AAT CTT GCT AGC CCT AGA TTT GGT TCT … in a sample. Which one of the following nomenclatures is the most appropriate one to describe this change?
A.c.4C>T(p.2Ala>Ser)
B.c.4C>T(p.Ala2Ser)
C.c.C4T(p.Ala2Ser)
D.c.4C>T(a.2Ala>Ser)
E.None of the above

Answer 18

B.c.4C>T(p.Ala2Ser)

Question 19

A reference sequence in the table below is mutated to … cag ATG [T]CC AAT CTT GCT AGC CCT AGA TTT GGT TCT … in a sample. Which one of the following nomenclatures is the most appropriate one to describe this change?

Answer 19

C.c.4C>T(p.Ala2Ser)

Question 58

The patient had a C282Y and a H63D mutation in the HFE gene. Parental tests confirmed that the C282Y was from the mother, while H63D was from the father. Which one of the following nomenclatures is the most appropriate one for this patient? A. p.H63D/C282Y B. p.[H63D;C282Y] C. p.[H63D];[C282Y] D. p.[H63D(;)C282Y] E. p.[H63D pat]+[C282Y mat]

Answer 58

C. p.[H63D];[C282Y]

Question 59

A technologist analyzed a peripheral-blood sample with an assay for hereditary hemochromatosis in a clinical molecular genetic laboratory. The patient had a C282Y and a H63D mutation in the HFE gene. Parental tests have not been done. Which one of the following nomenclatures is the most appropriate one for this patient? A. p.H63D/C282Y B. p.[H63D;C282Y] C. p.[H63D];[C282Y] D. p.[H63D(;)C282Y] E. p.[H63D pat]+[C282Y mat]

Answer 59

D. p.[H63D(;)C282Y]

Question 60

A technologist analyzed a peripheral-blood sample with an assay for hereditary hemochromatosis in a clinical molecular genetic laboratory. The patient had a C282Y and a H63D mutation in the HFE gene. Parental tests confirmed that both C282Y and H63D were maternal in origin. Which one of the following is the most appropriate nomenclature? A. p.H63D/C282Y B. p.[H63D;C282Y] C. p.[H63D];[C282Y] D. p.[H63D(;)C282Y] E. p.[H63D pat]+[C282Y mat]

Answer 60

B. p.[H63D;C282Y]

Question 61

Fragile X molecular testing was ordered for a 4-year-old boy with mental retardation. PCR and Southern blot methods were used for the analysis, and they detected one methylated allele with approximately 1000 CGG repeats. Which one of the following nomenclatures is the most appropriate to describe this change? A. c.-129CGG[1000] B. c.-129CGG(1000) C. c.-129CGG[1000];[0] D. c.-129CGG(1000);[0] E. c.-129CGG(1000);(1000)

Answer 61

B. c.-129CGG(1000)

Question 62

A cystic fibrosis (CF) mutation panel was performed on a pregnant woman. The results showed an R117H mutation with a 5T allele. The parental tests confirmed that both of the variants were maternal in origin. Which one of the following nomenclatures is the most appropriate one to describe these changes? A. c.[350G>A(;)1210-12T[5]] B. c.[350G>A;1210-12T[5]] C. c.[350G>A];[1210-12T[5]] D. c.[350G>A];[(1210-12T[5])] E. c.[350G>A(;)1210-12[5]] F. c.[350G>A(;)1210-7_1210-6delTT]

Answer 62

B. c.[350G>A;1210-12T[5]]

Question 63

A cystic fibrosis (CF) mutation panel was performed on a pregnant woman. The results showed an R117H mutation with a 5T allele. The parental tests confirmed that R117H was maternal in origin while 5T was paternal in origin. Which one of the following nomenclatures is the most appropriate one to describe these changes? A. c.[350G>A(;)1210-12T[5]] B. c.[350G>A;1210-12T[5]] C. c.[350G>A];[1210-12T[5]] D. c.[350G>A(;)1210-12[5]] E. c.[350G>A(;)1210-12[5]] F. c.[350G>A;1210-12[5]]

Answer 63

C. c.[350G>A];[1210-12T[5]]

Question 64

A cystic fibrosis (CF) mutation panel was performed on a pregnant woman. The results showed an R117H mutation with a 5T allele. The parental tests have not been done. Which one of the following nomenclatures is the most appropriate one to describe these changes? A. c.[350G>A(;)1210-12T[5]] B. c.[350G>A;1210-12T[5]] C. c.[350G>A];[1210-12T[5]] D. c.[350G>A(;)1210-12[5]] E. c.[350G>A(;)1210-12[5]] F. c.[350G>A;1210-12[5]]

Answer 64

A. c.[350G>A(;)1210-12T[5]]

Question 65

A cystic fibrosis (CF) mutation panel was performed on a pregnant woman. The results showed a homozygous deltaF508 mutation. The parental tests have not been done. Which one of the following A. c.[1521_1523delCTT];[1521_1523delCTT] B. c.[1521_1523delCTT];[(1521_1523delCTT)] C. c.[(1521_1523delCTT)];[(1521_1523delCTT)] D. c.[1521_1523delCTT];[=] E. c.[1521_1523delCTT];[0] F. None of the above

Answer 65

B. c.[1521_1523delCTT];[(1521_1523delCTT)]

Question 66

A cystic fibrosis (CF) mutation panel was performed on a pregnant woman. The results showed a heterozygous deltaF508 mutation.Which one of the following nomenclatures is the most appropriate one to describe this change? A. c.[1521_1523delCTT];[1521_1523delCTT] B. c.[1521_1523delCTT];[(1521_1523delCTT)] C. c.[(1521_1523delCTT)];[(1521_1523delCTT)] D. c.[1521_1523delCTT];[=] E. c.[1521_1523delCTT];[0] F. None of the above

Answer 66

D. c.[1521_1523delCTT];[=]

Question 76

A reference sequence in the table below is mutated to … cag GGA GCC GCA [GCT] AGC CCT AGA TTT GGT TCT gtt tta … in a sample. Which one of the following nomenclatures is the most appropriate one to describe this change? A. c.342_344del(p.Ala114del) B. c.343_345del(p.Ala114_Ala115delinsAla) C. c.343_345del(p.[Ala114=;Ala115del]) D. c.344_346del (p.Ala114_Ala115delinsAla) E. c.344_346del(p.[Ala114=;Ala115del]) F. c.345_347del(p.Ala115del)

Answer 76

F. c.345_347del(p.Ala115del)

Question 77

A reference sequence in the table below is mutated to … cag GGA GCC GCA GCG [GCT GCT] AGC CCT AGA TTT GGT TCT gtt tta … in a sample. Which one of the following nomenclatures is the most appropriate one to describe this change? A. c.344_345insGCT(p.Ala114_Ala115insAla) B. c.347_348insGCT(p.Ala115_Ser116insAla) C. c.345dupGCT(p.Ala115dup) D. c.345_347dupGCT(p.Ala115dupAla) E. None of the above

Answer 77

C. c.345dupGCT(p.Ala115dup)

Question 78

A reference sequence in the table below is mutated to … ca[a] ATG GCC AAT CTT GCT AGC CCT AGA TTT GGT TCT … in a sample. Which one of the following nomenclatures is the most appropriate one to describe this change? A. c.-1G>A(p.Met1ext) B. c.1-1G>A(p.-1fs) C. c.-1G>A(p.-1fs) D. c.-1G>A E. None of the above

Answer 78

D. c.-1G>A

Question 79

A reference sequence in the table below is the last exon of a gene, which is mutated to … cag GGA GCC AAT CTT GCT AGC CCT AGA TTT GGT TAG [a]tt tga gca… in a sample. Which one of the following nomenclatures is the most appropriate one to describe this change? A. c.*+1G>A B. c.362+4G>A(p.Ter121ext) C. c.*1G>A D. c.365+1G>A E. c.+1G>A(p.*121ext*?)

Answer 79

C. c.*1G>A