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NM_000059.4(BRCA2):c.516+2T>A AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 16, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002336176.10

Allele description [Variation Report for NM_000059.4(BRCA2):c.516+2T>A]

NM_000059.4(BRCA2):c.516+2T>A

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.516+2T>A
HGVS:
  • NC_000013.11:g.32326284T>A
  • NG_012772.3:g.15805T>A
  • NM_000059.4:c.516+2T>AMANE SELECT
  • NM_001406719.1:c.516+2T>A
  • NM_001406720.1:c.516+2T>A
  • NM_001406721.1:c.516+2T>A
  • NM_001406722.1:c.147+2T>A
  • LRG_293t1:c.516+2T>A
  • LRG_293:g.15805T>A
  • NC_000013.10:g.32900421T>A
  • NM_000059.3:c.516+2T>A
Links:
dbSNP: rs397507764
NCBI 1000 Genomes Browser:
rs397507764
Molecular consequence:
  • NM_000059.4:c.516+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406719.1:c.516+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406720.1:c.516+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406721.1:c.516+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406722.1:c.147+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002644887Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Dec 16, 2022) 		germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population.

Meindl A; German Consortium for Hereditary Breast and Ovarian Cancer..

Int J Cancer. 2002 Feb 1;97(4):472-80.

PubMed [citation]
PMID:
11802209

Differentiating pathogenic mutations from polymorphic alterations in the splice sites of BRCA1 and BRCA2.

Claes K, Poppe B, Machackova E, Coene I, Foretova L, De Paepe A, Messiaen L.

Genes Chromosomes Cancer. 2003 Jul;37(3):314-20.

PubMed [citation]
PMID:
12759930
See all PubMed Citations (9)

Details of each submission

From Ambry Genetics, SCV002644887.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

The c.516+2T>A intronic pathogenic mutation results from a T to A substitution two nucleotides after coding exon 5 in the BRCA2 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. RNA studies have demonstrated that this alteration as well as multiple other alterations impacting the same donor site result in abnormal splicing (Ambry internal data; Montalban G et al. Hum Mutat, 2019 12;40:2296-2317; Meindl A et al. Int J Cancer, 2002 Feb;97:472-80; Houdayer C et al. Hum Mutat, 2012 Aug;33:1228-38; Hansen TV et al. Breast Cancer Res Treat, 2010 Feb;119:547-50; Claes K et al. Genes Chromosomes Cancer, 2003 Jul;37:314-20; Whiley PJ et al. Hum Mutat, 2011 Jun;32:678-87; Fraile-Bethencourt E et al. J Pathol, 2019 08;248:409-420; Rodríguez-Balada M et al. Cancer Genet, 2016 Nov;209:487-492.) Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Oct 26, 2024