NM_007294.4(BRCA1):c.2500G>C (p.Gly834Arg) AND Hereditary cancer-predisposing syndrome

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Mar 16, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000164931.5

Allele description [Variation Report for NM_007294.4(BRCA1):c.2500G>C (p.Gly834Arg)]

NM_007294.4(BRCA1):c.2500G>C (p.Gly834Arg)

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.2500G>C (p.Gly834Arg)
HGVS:
  • NC_000017.11:g.43093031C>G
  • NG_005905.2:g.124953G>C
  • NM_007294.3:c.2500G>C
  • NM_007294.4:c.2500G>CMANE SELECT
  • NM_007297.4:c.2359G>C
  • NM_007298.3:c.787+1713G>C
  • NM_007299.4:c.787+1713G>C
  • NM_007300.4:c.2500G>C
  • NP_009225.1:p.Gly834Arg
  • NP_009225.1:p.Gly834Arg
  • NP_009228.2:p.Gly787Arg
  • NP_009231.2:p.Gly834Arg
  • LRG_292t1:c.2500G>C
  • LRG_292:g.124953G>C
  • LRG_292p1:p.Gly834Arg
  • NC_000017.10:g.41245048C>G
  • NR_027676.2:n.2677G>C
  • p.G834R
Protein change:
G787R
Links:
dbSNP: rs786202215
NCBI 1000 Genomes Browser:
rs786202215
Molecular consequence:
  • NM_007298.3:c.787+1713G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007299.4:c.787+1713G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007294.3:c.2500G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007294.4:c.2500G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007297.4:c.2359G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007300.4:c.2500G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_027676.2:n.2677G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
1

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MedGen: C0027672

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000215620Ambry Geneticscriteria provided, single submitter
Likely benign
(Nov 25, 2019)
germlineclinical testing

Citation Link,

SCV001340806Color Health, Inccriteria provided, single submitter
Uncertain significance
(Mar 16, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Description

This missense variant replaces glycine with arginine at codon 834 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/251008 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

SCV001340806

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Ambry Genetics, SCV000215620.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

In silico models in agreement (benign);Other strong data supporting benign classification

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

From Color Health, Inc, SCV001340806.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 7, 2021

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