U.S. flag

An official website of the United States government

NM_000059.4(BRCA2):c.2836_2837del (p.Asp946fs) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Feb 15, 2021
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000162914.15

Allele description [Variation Report for NM_000059.4(BRCA2):c.2836_2837del (p.Asp946fs)]

NM_000059.4(BRCA2):c.2836_2837del (p.Asp946fs)

Gene:
BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
13q13.1
Genomic location:
Preferred name:
NM_000059.4(BRCA2):c.2836_2837del (p.Asp946fs)
Other names:
3064delGA
HGVS:
  • NC_000013.11:g.32337191_32337192del
  • NG_012772.3:g.26712_26713del
  • NM_000059.4:c.2836_2837delMANE SELECT
  • NP_000050.3:p.Asp946fs
  • LRG_293:g.26712_26713del
  • NC_000013.10:g.32911327_32911328del
  • NC_000013.10:g.32911328_32911329del
  • NM_000059.3:c.2836_2837delGA
  • NM_000059.4:c.2836_2837del
  • U43746.1:n.3064_3065delGA
  • p.D946Ffs*12
Links:
Breast Cancer Information Core (BIC) (BRCA2): 3064&base_change=del GA; dbSNP: rs80359357
NCBI 1000 Genomes Browser:
rs80359357
Molecular consequence:
  • NM_000059.4:c.2836_2837del - frameshift variant - [Sequence Ontology: SO:0001589]
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; MeSH: D009386; MedGen: C0027672

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000213401Ambry Genetics
criteria provided, single submitter

(Ambry Autosomal Dominant and X-Linked criteria (3/2017))		Pathogenic
(Sep 11, 2018) 		germlineclinical testing

Citation Link,

SCV000906893Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Feb 15, 2021) 		germlineclinical testing

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

Help

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, SCV000213401.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The c.2836_2837delGA pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of two nucleotides at nucleotide positions 2836 to 2837, causing a translational frameshift with a predicted alternate stop codon (p.D946Ffs*12). This mutation was identified in a patient diagnosed with prostate cancer at age 51 (Kote-Jarai, Z et al. Br J Cancer. 2011 Oct 11;105(8):1230-4) and a patient with triple-negative breast cancer unselected for family history (Couch Fj et al. J Clin Oncol. 2015 Feb 1;33(4):304-11). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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

From Color Diagnostics, LLC DBA Color Health, SCV000906893.3

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

Description

This variant deletes 2 nucleotides in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with breast cancer (PMID: 25452441, 26681682, 27153395) or prostate cancer (PMID: 21952622). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

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

Last Updated: Oct 26, 2024