NM_000059.4(BRCA2):c.6025C>T (p.Gln2009Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 15, 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:: RCV000213281.13

Allele description [Variation Report for NM_000059.4(BRCA2):c.6025C>T (p.Gln2009Ter)]

NM_000059.4(BRCA2):c.6025C>T (p.Gln2009Ter)

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.6025C>T (p.Gln2009Ter)

HGVS:

NC_000013.11:g.32340380C>T
NG_012772.3:g.29901C>T
NM_000059.4:c.6025C>TMANE SELECT
NP_000050.2:p.Gln2009Ter
NP_000050.3:p.Gln2009Ter
LRG_293t1:c.6025C>T
LRG_293:g.29901C>T
LRG_293p1:p.Gln2009Ter
NC_000013.10:g.32914517C>T
NM_000059.3:c.6025C>T
U43746.1:n.6253C>T

Protein change:

Q2009*

Links:

dbSNP: rs80358838

NCBI 1000 Genomes Browser:

rs80358838

Molecular consequence:

NM_000059.4:c.6025C>T - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000278049	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Mar 19, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16284991, 27082205 Citation Link,
SCV004362140	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 15, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16284991, 27082205, 29084914, 32451972, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000278049

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Mar 19, 2019)

germline

clinical testing

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

Citation Link,

SCV004362140

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 15, 2023)

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

BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases.

Pal T, Permuth-Wey J, Betts JA, Krischer JP, Fiorica J, Arango H, LaPolla J, Hoffman M, Martino MA, Wakeley K, Wilbanks G, Nicosia S, Cantor A, Sutphen R.

Cancer. 2005 Dec 15;104(12):2807-16.

PubMed [citation]

PMID:: 16284991

Identification of novel BRCA founder mutations in Middle Eastern breast cancer patients using capture and Sanger sequencing analysis.

Bu R, Siraj AK, Al-Obaisi KA, Beg S, Al Hazmi M, Ajarim D, Tulbah A, Al-Dayel F, Al-Kuraya KS.

Int J Cancer. 2016 Sep 1;139(5):1091-7. doi: 10.1002/ijc.30143. Epub 2016 May 3.

PubMed [citation]

PMID:: 27082205
PMCID:: PMC5111783

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000278049.7

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

Description

The p.Q2009* pathogenic mutation (also known as c.6025C>T), located in coding exon 10 of the BRCA2 gene, results from a C to T substitution at nucleotide position 6025. This changes the amino acid from a glutamine to a stop codon within coding exon 10. This mutation has been reported in multiple individuals with breast and/or ovarian cancer (Pal T et al. Cancer. 2005 Dec;104:2807-16; Bu R et al. Int. J. Cancer. 2016 Sep;139:1091-7; Labidi-Galy SI et al. Clin Cancer Res. 2018 Jan 15;24(2):326-333; 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, SCV004362140.1

#	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 11 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 reported in individuals affected with breast or ovarian cancer (PMID: 16284991, 27082205, 29084914, 32451972). 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: Nov 10, 2024

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