NM_007294.4(BRCA1):c.5402G>A (p.Gly1801Asp) AND not specified

Clinical significance:Benign/Likely benign (Last evaluated: Jan 30, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000160007.4

Allele description [Variation Report for NM_007294.4(BRCA1):c.5402G>A (p.Gly1801Asp)]

NM_007294.4(BRCA1):c.5402G>A (p.Gly1801Asp)

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.5402G>A (p.Gly1801Asp)
Other names:
p.G1801D:GGC>GAC
HGVS:
  • NC_000017.11:g.43049125C>T
  • NG_005905.2:g.168859G>A
  • NM_007294.3:c.5402G>A
  • NM_007294.4:c.5402G>AMANE SELECT
  • NM_007297.4:c.5261G>A
  • NM_007298.3:c.2090G>A
  • NM_007299.4:c.2021-1422G>A
  • NM_007300.4:c.5465G>A
  • NP_009225.1:p.Gly1801Asp
  • NP_009225.1:p.Gly1801Asp
  • NP_009228.2:p.Gly1754Asp
  • NP_009229.2:p.Gly697Asp
  • NP_009231.2:p.Gly1822Asp
  • LRG_292t1:c.5402G>A
  • LRG_292:g.168859G>A
  • LRG_292p1:p.Gly1801Asp
  • NC_000017.10:g.41201142C>T
  • NR_027676.2:n.5579G>A
  • p.G1801D
Protein change:
G1754D
Links:
dbSNP: rs531210457
NCBI 1000 Genomes Browser:
rs531210457
Molecular consequence:
  • NM_007299.4:c.2021-1422G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007294.3:c.5402G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007294.4:c.5402G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007297.4:c.5261G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007298.3:c.2090G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007300.4:c.5465G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_027676.2:n.5579G>A - 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
SCV000210218GeneDxcriteria provided, single submitter
Likely benign
(Apr 4, 2017)
germlineclinical testing

Citation Link,

SCV001337979Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Benign
(Jan 30, 2021)
germlineclinical testing

PubMed (5)
[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
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

BRCA1/BRCA2 gene mutations/SNPs and BRCA1 haplotypes in early-onset breast cancer patients of Indian ethnicity.

Juwle A, Saranath D.

Med Oncol. 2012 Dec;29(5):3272-81. doi: 10.1007/s12032-012-0294-9. Epub 2012 Jul 3.

PubMed [citation]
PMID:
22752604

Patterns and functional implications of rare germline variants across 12 cancer types.

Lu C, Xie M, Wendl MC, Wang J, McLellan MD, Leiserson MD, Huang KL, Wyczalkowski MA, Jayasinghe R, Banerjee T, Ning J, Tripathi P, Zhang Q, Niu B, Ye K, Schmidt HK, Fulton RS, McMichael JF, Batra P, Kandoth C, Bharadwaj M, Koboldt DC, et al.

Nat Commun. 2015 Dec 22;6:10086. doi: 10.1038/ncomms10086.

PubMed [citation]
PMID:
26689913
PMCID:
PMC4703835
See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV000210218.9

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001337979.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

Variant summary: BRCA1 c.5402G>A (p.Gly1801Asp) results in a non-conservative amino acid change located in the BRCT domain (IPR001357) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251420 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.5402G>A has been reported in the literature in individuals affected with breast and ovarian cancer (e.g. Mehta_2018, Manie_2016) and as an unclassified variant in at-least two relatives of patients with early-onset breast cancer (Juwle_2012) without strong evidence of causality. These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. At least two publications report experimental evidence evaluating an impact on homology directed repair (HDR) activity (example, Lu_2015, Findlay_2018). Both studies no impact of this variant on HDR activity. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.

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

Last Updated: Jun 14, 2021

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