NM_000059.4(BRCA2):c.9709_9713del (p.Arg3237fs) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 19, 2022
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:: RCV003055711.3

Allele description [Variation Report for NM_000059.4(BRCA2):c.9709_9713del (p.Arg3237fs)]

NM_000059.4(BRCA2):c.9709_9713del (p.Arg3237fs)

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.9709_9713del (p.Arg3237fs)

HGVS:

NC_000013.11:g.32398222_32398226del
NG_012772.3:g.87743_87747del
NM_000059.4:c.9709_9713delMANE SELECT
NM_001406719.1:c.9613_9617delAGGAA
NM_001406720.1:c.9658_9662delAGGAA
NM_001406721.1:c.4777_4781delAGGAA
NM_001406722.1:c.3292_3296delAGGAA
NP_000050.2:p.Arg3237Valfs
NP_000050.3:p.Arg3237fs
NP_001393648.1:p.Arg3205Valfs
NP_001393649.1:p.Arg3220Valfs
NP_001393650.1:p.Arg1593Valfs
NP_001393651.1:p.Arg1098Valfs
LRG_293t1:c.9709_9713del
LRG_293:g.87743_87747del
LRG_293p1:p.Arg3237Valfs
NC_000013.10:g.32972357_32972361del
NC_000013.10:g.32972359_32972363del
NM_000059.3:c.9709_9713delAGGAA
NR_176251.1:n.9972_9976delAGGAA

Protein change:

R3237fs

Molecular consequence:

NM_000059.4:c.9709_9713del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406719.1:c.9613_9617delAGGAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406720.1:c.9658_9662delAGGAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406721.1:c.4777_4781delAGGAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406722.1:c.3292_3296delAGGAA - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary breast ovarian cancer syndrome
Synonyms:: Hereditary breast and ovarian cancer syndrome; Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145

Recent activity

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602573644F1 NIH_MGC_77 Homo sapiens cDNA clone IMAGE:4701755 5', mRNA sequence
602573644F1 NIH_MGC_77 Homo sapiens cDNA clone IMAGE:4701755 5', mRNA sequence
gi|13544978|gnl|dbEST|8251011|gb|BG 3.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003353401	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 19, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17026620, 18593900, 18607349, 22711857, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003353401

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 19, 2022)

germline

clinical testing

PubMed (5)
[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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Inherited association of breast and colorectal cancer: limited role of CHEK2 compared with high-penetrance genes.

Naseem H, Boylan J, Speake D, Leask K, Shenton A, Lalloo F, Hill J, Trump D, Evans DG.

Clin Genet. 2006 Nov;70(5):388-95.

PubMed [citation]

PMID:: 17026620

A syngeneic variance library for functional annotation of human variation: application to BRCA2.

Hucl T, Rago C, Gallmeier E, Brody JR, Gorospe M, Kern SE.

Cancer Res. 2008 Jul 1;68(13):5023-30. doi: 10.1158/0008-5472.CAN-07-6189.

PubMed [citation]

PMID:: 18593900
PMCID:: PMC2536704

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003353401.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the BRCA2 protein in which other variant(s) (p.Tyr3308*) have been determined to be pathogenic (PMID: 17026620, 18593900, 18607349, 22711857). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg3237Valfs*16) in the BRCA2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 182 amino acid(s) of the BRCA2 protein.

#	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: Sep 29, 2024

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