NM_007294.4(BRCA1):c.2481A>C (p.Glu827Asp) AND Hereditary breast and ovarian cancer syndrome

Clinical significance:Uncertain significance (Last evaluated: Mar 18, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001345360.1

Allele description [Variation Report for NM_007294.4(BRCA1):c.2481A>C (p.Glu827Asp)]

NM_007294.4(BRCA1):c.2481A>C (p.Glu827Asp)

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.2481A>C (p.Glu827Asp)
HGVS:
  • NC_000017.11:g.43093050T>G
  • NG_005905.2:g.124934A>C
  • NM_007294.3:c.2481A>C
  • NM_007294.4:c.2481A>CMANE SELECT
  • NM_007297.4:c.2340A>C
  • NM_007298.3:c.787+1694A>C
  • NM_007299.4:c.787+1694A>C
  • NM_007300.4:c.2481A>C
  • NP_009225.1:p.Glu827Asp
  • NP_009225.1:p.Glu827Asp
  • NP_009228.2:p.Glu780Asp
  • NP_009231.2:p.Glu827Asp
  • LRG_292t1:c.2481A>C
  • LRG_292:g.124934A>C
  • LRG_292p1:p.Glu827Asp
  • NC_000017.10:g.41245067T>G
  • NR_027676.2:n.2658A>C
Nucleotide change:
2600A>C
Protein change:
E780D
Links:
dbSNP: rs397508970
NCBI 1000 Genomes Browser:
rs397508970
Molecular consequence:
  • NM_007298.3:c.787+1694A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007299.4:c.787+1694A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007294.3:c.2481A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007294.4:c.2481A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007297.4:c.2340A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007300.4:c.2481A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_027676.2:n.2658A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Hereditary breast and ovarian cancer syndrome (HBOC)
Synonyms:
Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC)
Identifiers:
MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145; OMIM: PS604370

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001539471Invitaecriteria provided, single submitter
Uncertain significance
(Mar 18, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod

Citations

PubMed

Mutation analysis of BRCA1 and BRCA2 from 793 Korean patients with sporadic breast cancer.

Han SH, Lee KR, Lee DG, Kim BY, Lee KE, Chung WS.

Clin Genet. 2006 Dec;70(6):496-501.

PubMed [citation]
PMID:
17100994

Evaluation of an amplicon-based next-generation sequencing panel for detection of BRCA1 and BRCA2 genetic variants.

Shin S, Hwang IS, Lee ST, Choi JR.

Breast Cancer Res Treat. 2016 Aug;158(3):433-40. doi: 10.1007/s10549-016-3891-z. Epub 2016 Jul 6.

PubMed [citation]
PMID:
27383479
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001539471.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces glutamic acid with aspartic acid at codon 827 of the BRCA1 protein (p.Glu827Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is present in population databases (rs397508970, ExAC 0.01%). This variant has been reported in individuals affected with breast cancer or hereditary breast and ovarian cancer syndrome (PMID: 17100994, 27383479). ClinVar contains an entry for this variant (Variation ID: 54580). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Jun 18, 2021

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