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NM_000059.4(BRCA2):c.7008-5T>C AND Hereditary cancer-predisposing syndrome

Germline classification:
Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:
Jul 25, 2022
Review status:
criteria provided, conflicting classifications
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:
RCV000575836.13

Allele description [Variation Report for NM_000059.4(BRCA2):c.7008-5T>C]

NM_000059.4(BRCA2):c.7008-5T>C

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.7008-5T>C
HGVS:
  • NC_000013.11:g.32354856T>C
  • NG_012772.3:g.44377T>C
  • NM_000059.4:c.7008-5T>CMANE SELECT
  • LRG_293t1:c.7008-5T>C
  • LRG_293:g.44377T>C
  • NC_000013.10:g.32928993T>C
  • NM_000059.3:c.7008-5T>C
Nucleotide change:
IVS13-5T>C
Links:
dbSNP: rs397507380
NCBI 1000 Genomes Browser:
rs397507380
Molecular consequence:
  • NM_000059.4:c.7008-5T>C - intron variant - [Sequence Ontology: SO:0001627]

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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000668821Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)
Likely benign
(Mar 15, 2021)
germlineclinical testing

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

Citation Link,

SCV000689025Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Jul 25, 2022)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV002536291Sema4, Sema4
criteria provided, single submitter

(Sema4 Curation Guidelines)
Uncertain significance
(Sep 7, 2021)
germlinecuration

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

Citation Link

Summary from all submissions

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

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

Minigene Splicing Assays Identify 12 Spliceogenic Variants of BRCA2 Exons 14 and 15.

Fraile-Bethencourt E, Valenzuela-Palomo A, Díez-Gómez B, Caloca MJ, Gómez-Barrero S, Velasco EA.

Front Genet. 2019;10:503. doi: 10.3389/fgene.2019.00503.

PubMed [citation]
PMID:
31191615
PMCID:
PMC6546720

Details of each submission

From Ambry Genetics, SCV000668821.5

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

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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

From Color Diagnostics, LLC DBA Color Health, SCV000689025.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This variant causes a T to C nucleotide substitution at the -5 position of intron 13 of the BRCA2 gene. A RNA study reported that this variant did not impact splicing in a minigene splicing assay (PMID: 31191615). This variant has been detected in individuals affected with BRCA2-associated cancers and relevant family history (Color internal data). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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

From Sema4, Sema4, SCV002536291.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 15, 2024