NM_000059.4(BRCA2):c.3717del (p.Lys1239fs) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Feb 28, 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:: RCV000486579.17

Allele description [Variation Report for NM_000059.4(BRCA2):c.3717del (p.Lys1239fs)]

NM_000059.4(BRCA2):c.3717del (p.Lys1239fs)

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.3717del (p.Lys1239fs)

HGVS:

NC_000013.10:g.32912207del
NC_000013.11:g.32338072del
NG_012772.3:g.27593del
NM_000059.4:c.3717delMANE SELECT
NP_000050.3:p.Lys1239fs
LRG_293:g.27593del
NC_000013.10:g.32912207del
NC_000013.10:g.32912209del
NC_000013.10:g.32912209delA
NC_000013.11:g.32338072delA
NM_000059.3:c.3717delA
NM_000059.4:c.3717del
U43746.1:n.3945delA
p.K1239NFS*20
p.Lys1239Asnfs*20

Nucleotide change:

3945delA

Links:

Breast Cancer Information Core (BIC) (BRCA2): 3945&base_change=del A; dbSNP: rs80359401

NCBI 1000 Genomes Browser:

rs80359401

Molecular consequence:

NM_000059.4:c.3717del - 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
SCV000566557	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Feb 28, 2023)	germline	clinical testing	Citation Link,
SCV000889032	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Sep 15, 2022)	unknown	clinical testing	PubMed (7) [See all records that cite these PMIDs] 15131399, 18042939, 29446198, 17592676, 19620486, 33471991, 26467025
SCV003815025	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 17, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000566557

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Feb 28, 2023)

germline

clinical testing

Citation Link,

SCV000889032

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Sep 15, 2022)

unknown

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

SCV003815025

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 17, 2022)

germline

clinical testing

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

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
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Cancer variation associated with the position of the mutation in the BRCA2 gene.

Lubinski J, Phelan CM, Ghadirian P, Lynch HT, Garber J, Weber B, Tung N, Horsman D, Isaacs C, Monteiro AN, Sun P, Narod SA.

Fam Cancer. 2004;3(1):1-10.

PubMed [citation]

PMID:: 15131399

Breast cancer risk among male BRCA1 and BRCA2 mutation carriers.

Tai YC, Domchek S, Parmigiani G, Chen S.

J Natl Cancer Inst. 2007 Dec 5;99(23):1811-4. Epub 2007 Nov 27.

PubMed [citation]

PMID:: 18042939
PMCID:: PMC2267289

See all PubMed Citations (8)

Details of each submission

From GeneDx, SCV000566557.5

#	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 3945delA; This variant is associated with the following publications: (PMID: 15131399, 25673166, 18042939, 19620486, 17592676, 29446198, 32918181, 30787465, 33087929, 31892343, 31853058)

#	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, SCV000889032.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

It 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 and/or family history of breast cancer (PMID: 33471991 (2021), 17592676 (2007), 18042939 (2007), and 15131399 (2004)). 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

From Revvity Omics, Revvity, SCV003815025.2

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

#	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: Oct 26, 2024

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