NM_000059.4(BRCA2):c.2145A>G (p.Gly715=) AND Breast-ovarian cancer, familial 2

Clinical significance:Benign (Last evaluated: Jun 29, 2017)

Review status:3 stars out of maximum of 4 stars

reviewed by expert panel

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000495123.4

Allele description [Variation Report for NM_000059.4(BRCA2):c.2145A>G (p.Gly715=)]

NM_000059.4(BRCA2):c.2145A>G (p.Gly715=)

Gene:
BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q13.1
Genomic location:
Preferred name:
NM_000059.4(BRCA2):c.2145A>G (p.Gly715=)
Other names:
p.G715G:GGA>GGG
HGVS:
  • NC_000013.11:g.32336500A>G
  • NG_012772.3:g.26021A>G
  • NM_000059.3:c.2145A>G
  • NM_000059.4:c.2145A>GMANE SELECT
  • NP_000050.2:p.Gly715=
  • NP_000050.3:p.Gly715=
  • LRG_293t1:c.2145A>G
  • LRG_293:g.26021A>G
  • LRG_293p1:p.Gly715=
  • NC_000013.10:g.32910637A>G
  • p.G715G
  • p.Gly715Gly
Links:
dbSNP: rs112566179
NCBI 1000 Genomes Browser:
rs112566179
Molecular consequence:
  • NM_000059.3:c.2145A>G - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_000059.4:c.2145A>G - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:
Breast-ovarian cancer, familial 2 (BROVCA2)
Synonyms:
BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 2; BREAST CANCER, FAMILIAL, SUSCEPTIBILITY TO, 2; Breast cancer, familial 2
Identifiers:
MONDO: MONDO:0012933; MedGen: C2675520; Orphanet: 145; OMIM: 612555

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000578023Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)reviewed by expert panel
Benign
(Jun 29, 2017)
germlinecuration

Citation Link,

SCV001549664Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria providedLikely benignunknownclinical testing

Summary from all submissions

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

Details of each submission

From Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA), SCV000578023.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

Synonymous substitution variant, with low bioinformatic likelihood to alter mRNA splicing (splicing prior 0.02; http://priors.hci.utah.edu/PRIORS/) and frequency 0.0014 (African), derived from ExAC (2014-12-17).

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

From Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001549664.1

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

Description

The BRCA2 p.Gly715= variant was identified in 1 of 820 proband chromosomes (frequency: 0.001) from individuals or families with breast cancer (Fackenthal 2012). The variant was also identified in dbSNP (ID: rs112566179) as "With other allele", ClinVar (classified as benign by Invitae, GeneDx, Color and ENIGMA; as likely benign by three submitters), LOVD 3.0 (3x), and in UMD-LSDB (4x as unclassified variant). The variant was identified in UMD-LSDB with a co-occurring pathogenic BRCA2 variant (c.6159delT, p.Ala2054Leufs*16), increasing the likelihood that the p.Gly715= variant does not have clinical significance. The variant was identified in control databases in 43 of 277062 chromosomes at a frequency of 0.0002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 42 of 24028 chromosomes (freq: 0.002) and Latino in 1 of 34366 chromosomes (freq: 0.00003), while the variant was not observed in the Other, European, Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. The p.Gly715= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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

Last Updated: Nov 10, 2021

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