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NM_000059.4(BRCA2):c.67+1G>A AND not provided

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Jan 31, 2023
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:
RCV000218090.10

Allele description [Variation Report for NM_000059.4(BRCA2):c.67+1G>A]

NM_000059.4(BRCA2):c.67+1G>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.67+1G>A
HGVS:
  • NC_000013.11:g.32316528G>A
  • NG_012772.3:g.6049G>A
  • NG_017006.2:g.3836C>T
  • NM_000059.4:c.67+1G>AMANE SELECT
  • NM_001406719.1:c.67+1G>A
  • NM_001406720.1:c.67+1G>A
  • NM_001406721.1:c.67+1G>A
  • NM_001406722.1:c.-303+861G>A
  • LRG_293t1:c.67+1G>A
  • LRG_293:g.6049G>A
  • NC_000013.10:g.32890665G>A
  • NM_000059.3:c.67+1G>A
  • U43746.1:n.295+1G>A
Nucleotide change:
IVS2+1G>A
Links:
Breast Cancer Information Core (BIC) (BRCA2): 295+1&base_change=G to A; dbSNP: rs81002796
NCBI 1000 Genomes Browser:
rs81002796
Molecular consequence:
  • NM_001406722.1:c.-303+861G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000059.4:c.67+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406719.1:c.67+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406720.1:c.67+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406721.1:c.67+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000279587GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Pathogenic
(Nov 19, 2015) 		germlineclinical testing

Citation Link,

SCV004220516Quest Diagnostics Nichols Institute San Juan Capistrano
criteria provided, single submitter

(Quest Diagnostics criteria)		Pathogenic
(Jan 31, 2023) 		unknownclinical testing

PubMed (13)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Twenty-three novel BRCA1 and BRCA2 sequence alterations in breast and/or ovarian cancer families in Southern Germany.

Meyer P, Voigtlaender T, Bartram CR, Klaes R.

Hum Mutat. 2003 Sep;22(3):259.

PubMed [citation]
PMID:
12938098

Two BRCA1/2 founder mutations in Jews of Sephardic origin.

Sagi M, Eilat A, Ben Avi L, Goldberg Y, Bercovich D, Hamburger T, Peretz T, Lerer I.

Fam Cancer. 2011 Mar;10(1):59-63. doi: 10.1007/s10689-010-9395-9.

PubMed [citation]
PMID:
21063910
See all PubMed Citations (13)

Details of each submission

From GeneDx, SCV000279587.9

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

Description

This variant is denoted BRCA2 c.67+1G>A or IVS2+1G>A and consists of a G>A nucleotide substitution at the +1 position of intron 2 of the BRCA2 gene. This variant destroys a canonical splice donor site and causes exon 2 skipping, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product (Bonatti 2006). This variant, also defined as BRCA2 295+1G>A using alternate nomenclature, has been reported in individuals with a personal and family history of early-onset breast and/or ovarian cancer and has been described as a founder pathogenic variant in the Sephardic Jewish population (Bonatti 2006, Sagi 2011, Balabanski 2014). We consider this variant to be pathogenic.

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004220516.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (13)

Description

This variant disrupts a canonical splice-donor site and interferes with normal BRCA2 mRNA splicing. It is reported to cause the skipping of exon 2 during splicing, resulting in a truncated protein product (PMID: 17011978 (2006)). This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in individuals with a personal or family history of breast and/or ovarian cancer (PMIDs: 35220195 (2022), 32658311 (2021), 32599251 (2020), 32438681 (2020), 32058061 (2020), 32846166 (2020), 28888541 (2017), 21063910 (2011), and 12938098 (2003)). Based on the available information, this variant is classified as pathogenic.

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

Last Updated: Jun 2, 2024