NM_007294.4(BRCA1):c.124A>G (p.Ile42Val) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Oct 3, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001175357.1

Allele description [Variation Report for NM_007294.4(BRCA1):c.124A>G (p.Ile42Val)]

NM_007294.4(BRCA1):c.124A>G (p.Ile42Val)

Gene:
BRCA1:BRCA1 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.31
Genomic location:
Preferred name:
NM_007294.4(BRCA1):c.124A>G (p.Ile42Val)
HGVS:
  • NC_000017.11:g.43115736T>C
  • NG_005905.2:g.102248A>G
  • NM_007294.3:c.124A>G
  • NM_007294.4:c.124A>GMANE SELECT
  • NM_007297.4:c.-8+8281A>G
  • NM_007298.3:c.124A>G
  • NM_007299.4:c.124A>G
  • NM_007300.4:c.124A>G
  • NP_009225.1:p.Ile42Val
  • NP_009225.1:p.Ile42Val
  • NP_009229.2:p.Ile42Val
  • NP_009230.2:p.Ile42Val
  • NP_009231.2:p.Ile42Val
  • LRG_292t1:c.124A>G
  • LRG_292:g.102248A>G
  • LRG_292p1:p.Ile42Val
  • NC_000017.10:g.41267753T>C
  • NR_027676.2:n.326A>G
  • U14680.1:n.243A>G
Protein change:
I42V
Links:
dbSNP: rs80357163
NCBI 1000 Genomes Browser:
rs80357163
Molecular consequence:
  • NM_007297.4:c.-8+8281A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007294.3:c.124A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007294.4:c.124A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007298.3:c.124A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007299.4:c.124A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007300.4:c.124A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_027676.2:n.326A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Functional consequence:
functionally_normal [Sequence Ontology: SO:0002219] - Comment(s)

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000698840Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Oct 3, 2019)
germlineclinical testing

PubMed (11)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Analysis of missense variation in human BRCA1 in the context of interspecific sequence variation.

Abkevich V, Zharkikh A, Deffenbaugh AM, Frank D, Chen Y, Shattuck D, Skolnick MH, Gutin A, Tavtigian SV.

J Med Genet. 2004 Jul;41(7):492-507.

PubMed [citation]
PMID:
15235020
PMCID:
PMC1735826

Analysis of BRCA1 variants in double-strand break repair by homologous recombination and single-strand annealing.

Towler WI, Zhang J, Ransburgh DJ, Toland AE, Ishioka C, Chiba N, Parvin JD.

Hum Mutat. 2013 Mar;34(3):439-45. doi: 10.1002/humu.22251. Epub 2012 Dec 12.

PubMed [citation]
PMID:
23161852
PMCID:
PMC3906639
See all PubMed Citations (11)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000698840.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (11)

Description

Variant summary: BRCA1 c.124A>G (p.Ile42Val) results in a conservative amino acid change located in the RING-type zinc finger domain of the encoded protein sequence (IPR001841). Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250738 control chromosomes (gnomAD). To our knowledge, no occurrence of c.124A>G in individuals affected with Hereditary Breast and Ovarian Cancer has been reported in the literature. Several publications reported experimental evidence evaluating an impact on protein function and found that the I42V variant protein retains the E3 ligase-, SSA- and HDR activity; the variant does not impact BARD1- and UbcH5a binding, but slightly decreases cell survival upon radiation. Two ClinVar submissions (evaluation after 2014) cites the variant once as likely benign and once as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 14, 2021

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