NM_000059.4(BRCA2):c.115del (p.Ala39fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 13, 2024
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:: RCV000483184.13

Allele description [Variation Report for NM_000059.4(BRCA2):c.115del (p.Ala39fs)]

NM_000059.4(BRCA2):c.115del (p.Ala39fs)

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.115del (p.Ala39fs)

HGVS:

NC_000013.11:g.32319124del
NG_012772.3:g.8645del
NG_017006.2:g.1240del
NM_000059.4:c.115delMANE SELECT
NP_000050.3:p.Ala39fs
LRG_293:g.8645del
NC_000013.10:g.32893261del
NM_000059.3:c.115delG
p.Ala39Leufs*41

Links:

dbSNP: rs397507573

NCBI 1000 Genomes Browser:

rs397507573

Molecular consequence:

NM_000059.4:c.115del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000566556	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (May 13, 2024)	germline	clinical testing	Citation Link,
SCV000600467	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (May 28, 2022)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 26287763, 16683254, 19949876, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000566556

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(May 13, 2024)

germline

clinical testing

Citation Link,

SCV000600467

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(May 28, 2022)

unknown

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

A high frequency of BRCA mutations in young black women with breast cancer residing in Florida.

Pal T, Bonner D, Cragun D, Monteiro AN, Phelan C, Servais L, Kim J, Narod SA, Akbari MR, Vadaparampil ST.

Cancer. 2015 Dec 1;121(23):4173-80. doi: 10.1002/cncr.29645. Epub 2015 Aug 19.

PubMed [citation]

PMID:: 26287763
PMCID:: PMC4666784

A DGGE system for comprehensive mutation screening of BRCA1 and BRCA2: application in a Dutch cancer clinic setting.

van der Hout AH, van den Ouweland AM, van der Luijt RB, Gille HJ, Bodmer D, Brüggenwirth H, Mulder IM, van der Vlies P, Elfferich P, Huisman MT, ten Berge AM, Kromosoeto J, Jansen RP, van Zon PH, Vriesman T, Arts N, Lange MB, Oosterwijk JC, Meijers-Heijboer H, Ausems MG, Hoogerbrugge N, Verhoef S, et al.

Hum Mutat. 2006 Jul;27(7):654-66.

PubMed [citation]

PMID:: 16683254

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000566556.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 343delG; This variant is associated with the following publications: (PMID: 16683254, 19949876, 24013928, 26287763, 36922933)

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000600467.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The BRCA2 c.115del (p.Ala39Leufs*41) variant alters the translational reading frame of the BRCA2 mRNA and causes the premature termination of BRCA2 protein synthesis. This variant has been reported in the published literature in a woman affected with breast cancer (PMID: 26287763 (2015)) and in families affected with breast and/or ovarian cancer (PMIDs: 16683254 (2006), 19949876 (2010)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic.

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

Last Updated: Oct 26, 2024

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