NM_000059.4(BRCA2):c.7563C>A (p.Ile2521=) AND Breast-ovarian cancer, familial 2

Clinical significance:Likely 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:
RCV000495321.3

Allele description [Variation Report for NM_000059.4(BRCA2):c.7563C>A (p.Ile2521=)]

NM_000059.4(BRCA2):c.7563C>A (p.Ile2521=)

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.7563C>A (p.Ile2521=)
HGVS:
  • NC_000013.11:g.32356555C>A
  • NG_012772.3:g.46076C>A
  • NM_000059.3:c.7563C>A
  • NM_000059.4:c.7563C>AMANE SELECT
  • NP_000050.2:p.Ile2521=
  • NP_000050.3:p.Ile2521=
  • LRG_293t1:c.7563C>A
  • LRG_293:g.46076C>A
  • LRG_293p1:p.Ile2521=
  • NC_000013.10:g.32930692C>A
Links:
dbSNP: rs786204282
NCBI 1000 Genomes Browser:
rs786204282
Molecular consequence:
  • NM_000059.3:c.7563C>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_000059.4:c.7563C>A - synonymous variant - [Sequence Ontology: SO:0001819]
Observations:
1

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
SCV000578685Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)reviewed by expert panel
Likely benign
(Jun 29, 2017)
germlinecuration

Citation Link,

SCV001552588Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria providedUncertain significanceunknownclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration
not providedunknownyes1not providednot providednot providednot providedclinical testing

Details of each submission

From Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA), SCV000578685.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).

#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), SCV001552588.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The BRCA2 p.Ile2521= variant was not identified in the literature nor was it identified in the Cosmic, LOVD 3.0, UMD-LSDB, BIC Database, ARUP Laboratories, or Zhejiang University databases. The variant was also identified in dbSNP (ID: rs786204282) as "With other allele", ClinVar (classified as likely benign by Invitae, GeneDx, and ENIGMA; and as uncertain significance by COGR), and in GeneInsight-COGR database. The variant was identified in control databases in 1 of 245904 chromosomes at a frequency of 0.000004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the East Asian population in 1 of 17240 chromosomes (freq: 0.00006), while the variant was not observed in the African, Other, Latino, European, Ashkenazi Jewish, Finnish, or South Asian populations. The p.Ile2521= 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. The variant occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as uncertain significance.

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

Last Updated: May 23, 2021

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