NM_007294.4(BRCA1):c.1834A>G (p.Arg612Gly) AND Hereditary cancer-predisposing syndrome

Clinical significance:Uncertain significance (Last evaluated: Oct 14, 2019)

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:
RCV000221996.5

Allele description [Variation Report for NM_007294.4(BRCA1):c.1834A>G (p.Arg612Gly)]

NM_007294.4(BRCA1):c.1834A>G (p.Arg612Gly)

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.1834A>G (p.Arg612Gly)
HGVS:
  • NC_000017.11:g.43093697T>C
  • NG_005905.2:g.124287A>G
  • NM_007294.3:c.1834A>G
  • NM_007294.4:c.1834A>GMANE SELECT
  • NM_007297.4:c.1693A>G
  • NM_007298.3:c.787+1047A>G
  • NM_007299.4:c.787+1047A>G
  • NM_007300.4:c.1834A>G
  • NP_009225.1:p.Arg612Gly
  • NP_009225.1:p.Arg612Gly
  • NP_009228.2:p.Arg565Gly
  • NP_009231.2:p.Arg612Gly
  • LRG_292t1:c.1834A>G
  • LRG_292:g.124287A>G
  • LRG_292p1:p.Arg612Gly
  • NC_000017.10:g.41245714T>C
  • NR_027676.2:n.2011A>G
  • U14680.1:n.1953A>G
Protein change:
R565G
Links:
dbSNP: rs80357245
NCBI 1000 Genomes Browser:
rs80357245
Molecular consequence:
  • NM_007298.3:c.787+1047A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007299.4:c.787+1047A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007294.3:c.1834A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007294.4:c.1834A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007297.4:c.1693A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007300.4:c.1834A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_027676.2:n.2011A>G - 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
SCV000275535Ambry Geneticscriteria provided, single submitter
Uncertain significance
(Oct 14, 2019)
germlineclinical testing

Citation Link,

SCV000688349Color Health, Inccriteria provided, single submitter
Uncertain significance
(Apr 12, 2019)
germlineclinical testing

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

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, SCV000275535.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The p.R612G variant (also known as c.1834A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 1834. The arginine at codon 612 is replaced by glycine, an amino acid with dissimilar properties. Using a comparative evolutionary approach, multiple studies have predicted that this missense alteration affects protein function because it occurs at a conservative site (Fleming MA et al. Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1151-6; Burk-Herrick A et al. Mamm Genome. 2006 Mar;17(3):257-70; Ramirez CJ et al. Oncogene. 2004 Mar 4;23(9):1780-8). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

From Color Health, Inc, SCV000688349.3

#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: Nov 20, 2021

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