NM_000059.4(BRCA2):c.8948_8953+5del AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 14, 2020
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:: RCV000129964.13

Allele description [Variation Report for NM_000059.4(BRCA2):c.8948_8953+5del]

NM_000059.4(BRCA2):c.8948_8953+5del

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.8948_8953+5del

HGVS:

NC_000013.11:g.32379510_32379520del
NG_012772.3:g.69031_69041del
NM_000059.4:c.8948_8953+5delMANE SELECT
LRG_293t1:c.8948_8953+5del
LRG_293:g.69031_69041del
NC_000013.10:g.32953644_32953654del
NC_000013.10:g.32953647_32953657del
NM_000059.3:c.8948_8953+5del
NM_000059.3:c.8948_8953+5delATTCAGGTAAG
p.Asp2983_Ser2984del

Links:

dbSNP: rs276174915

NCBI 1000 Genomes Browser:

rs276174915

Molecular consequence:

NM_000059.4:c.8948_8953+5del - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000184788	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Feb 14, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25382762, 29446198 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000184788

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Feb 14, 2020)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Functional classification of BRCA2 DNA variants by splicing assays in a large minigene with 9 exons.

Acedo A, Hernández-Moro C, Curiel-García Á, Díez-Gómez B, Velasco EA.

Hum Mutat. 2015 Feb;36(2):210-21. doi: 10.1002/humu.22725.

PubMed [citation]

PMID:: 25382762
PMCID:: PMC4371643

Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.

Rebbeck TR, Friebel TM, Friedman E, Hamann U, Huo D, Kwong A, Olah E, Olopade OI, Solano AR, Teo SH, Thomassen M, Weitzel JN, Chan TL, Couch FJ, Goldgar DE, Kruse TA, Palmero EI, Park SK, Torres D, van Rensburg EJ, McGuffog L, Parsons MT, et al.

Hum Mutat. 2018 May;39(5):593-620. doi: 10.1002/humu.23406. Epub 2018 Mar 12.

PubMed [citation]

PMID:: 29446198
PMCID:: PMC5903938

Details of each submission

From Ambry Genetics, SCV000184788.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The c.8948_8953+5del11 intronic variant (also known as 9176del11), results from a deletion of 11 nucleotides between positions 8948 and 8953+5, which involves the canonical splice site after coding exon 21 of the BRCA2 gene. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site. Further, this alteration has been shown to result in aberrant splicing, using a minigene assay (Acedo A et al. Hum. Mutat., 2015 Feb;36:210-21). This alteration was also identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum. Mutat., 2018 05;39:593-620). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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