NM_000059.4(BRCA2):c.7878G>A (p.Trp2626Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 17, 2022
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:: RCV000217125.20

Allele description [Variation Report for NM_000059.4(BRCA2):c.7878G>A (p.Trp2626Ter)]

NM_000059.4(BRCA2):c.7878G>A (p.Trp2626Ter)

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.7878G>A (p.Trp2626Ter)

HGVS:

NC_000013.11:g.32362595G>A
NG_012772.3:g.52116G>A
NM_000059.4:c.7878G>AMANE SELECT
NP_000050.2:p.Trp2626Ter
NP_000050.3:p.Trp2626Ter
LRG_293t1:c.7878G>A
LRG_293:g.52116G>A
LRG_293p1:p.Trp2626Ter
NC_000013.10:g.32936732G>A
NM_000059.3:c.7878G>A
U43746.1:n.8106G>A
p.Trp2626*

Nucleotide change:

8106G>A

Protein change:

W2626*

Links:

dbSNP: rs80359013

NCBI 1000 Genomes Browser:

rs80359013

Molecular consequence:

NM_000059.4:c.7878G>A - nonsense - [Sequence Ontology: SO:0001587]

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

Recent activity

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nucleotide kinase [Staphylococcus phage phiPVL-CN125]
nucleotide kinase [Staphylococcus phage phiPVL-CN125]
gi|239507385|ref|YP_002939696.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000276739	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Nov 17, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21218378, 22970155, 25452441, 26187060 Citation Link,
SCV000906563	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 22, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 21218378, 25452441, 26187060, 33471991, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000276739

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Nov 17, 2022)

germline

clinical testing

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

Citation Link,

SCV000906563

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 22, 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

Identification of BRCA1/2 founder mutations in Southern Chinese breast cancer patients using gene sequencing and high resolution DNA melting analysis.

Kwong A, Ng EK, Wong CL, Law FB, Au T, Wong HN, Kurian AW, West DW, Ford JM, Ma ES.

PLoS One. 2012;7(9):e43994. doi: 10.1371/journal.pone.0043994. Epub 2012 Sep 7.

PubMed [citation]

PMID:: 22970155
PMCID:: PMC3436879

Detection of BRCA1 and BRCA2 mutations in a selected Hawaii population.

Carney ME, Basiliere MS, Mates K, Sing CK.

Hawaii Med J. 2010 Nov;69(11):268-71.

PubMed [citation]

PMID:: 21218378
PMCID:: PMC3071188

See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV000276739.8

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

Description

The p.W2626* pathogenic mutation (also known as c.7878G>A) located in coding exon 16 of the BRCA2 gene, results from a G to A substitution at nucleotide position 7878. This changes the amino acid from a tryptophan to a stop codon within coding exon 16. This alteration has been reported in multiple high-risk breast and/or ovarian cancer patients in the literature (Carney ME et al. Hawaii Med J. 2010 Nov;69:268-71; Couch FJ et al. J. Clin. Oncol. 2015 Feb;33:304-11; Kwong A et al. PLoS ONE. 2012 Sep;7:e43994; Kwong A et al. J. Med. Genet. 2016 Jan;53:15-23; Rebbeck TR et al. Hum Mutat. 2018 May;39(5):593-620). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted 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

From Color Diagnostics, LLC DBA Color Health, SCV000906563.5

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

Description

This variant changes 1 nucleotide in exon 17 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been detected in at least 10 individuals affected with breast cancer (PMID: 21218378, 25452441, 26187060, 33471991; Color internal data; Leiden Open Variation Database DB-ID BRCA2_005264) and one proband who also had cancer of the brain (PMID: 21218378). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

#	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 13, 2024

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