NM_000059.4(BRCA2):c.8878C>T (p.Gln2960Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 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:: RCV000162940.19

Allele description [Variation Report for NM_000059.4(BRCA2):c.8878C>T (p.Gln2960Ter)]

NM_000059.4(BRCA2):c.8878C>T (p.Gln2960Ter)

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.8878C>T (p.Gln2960Ter)

Other names:

9106C>T

HGVS:

NC_000013.11:g.32379440C>T
NG_012772.3:g.68961C>T
NM_000059.4:c.8878C>TMANE SELECT
NP_000050.2:p.Gln2960Ter
NP_000050.3:p.Gln2960Ter
LRG_293t1:c.8878C>T
LRG_293:g.68961C>T
LRG_293p1:p.Gln2960Ter
NC_000013.10:g.32953577C>T
NM_000059.3:c.8878C>T
U43746.1:n.9106C>T
p.Gln2960*
p.Q2960*

Protein change:

Q2960*

Links:

dbSNP: rs80359140

NCBI 1000 Genomes Browser:

rs80359140

Molecular consequence:

NM_000059.4:c.8878C>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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NP_RS12750 [Natronomonas pharaonis DSM 2160]
NP_RS12750 [Natronomonas pharaonis DSM 2160]
Gene ID:3703243

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000213427	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Aug 2, 2022)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 10449599, 16764716, 17224268, 18821011, 27425403, 28091860, 29161300 Citation Link,
SCV000684004	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 17, 2022)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 16982466, 17224268, 23165508, 28091860, 29446198, 30606148, 32438681, 33471991, 35281878, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000213427

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Aug 2, 2022)

germline

clinical testing

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

Citation Link,

SCV000684004

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 17, 2022)

germline

clinical testing

PubMed (10)
[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 genes: role in hereditary breast and ovarian cancer in Italy.

Santarosa M, Dolcetti R, Magri MD, Crivellari D, Tibiletti MG, Gallo A, Tumolo S, Della Puppa L, Furlan D, Boiocchi M, Viel A.

Int J Cancer. 1999 Sep 24;83(1):5-9.

PubMed [citation]

PMID:: 10449599

Phenotypic features and genetic characterization of male breast cancer families: identification of two recurrent BRCA2 mutations in north-east of Italy.

Miolo G, Puppa LD, Santarosa M, De Giacomi C, Veronesi A, Bidoli E, Tibiletti MG, Viel A, Dolcetti R.

BMC Cancer. 2006 Jun 9;6:156.

PubMed [citation]

PMID:: 16764716
PMCID:: PMC1586026

See all PubMed Citations (15)

Details of each submission

From Ambry Genetics, SCV000213427.7

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

Description

The p.Q2960* pathogenic mutation (also known as c.8878C>T), located in coding exon 21 of the BRCA2 gene, results from a C to T substitution at nucleotide position 8878. This changes the amino acid from a glutamine to a stop codon within coding exon 21. This mutation has been identified in multiple families with hereditary breast and ovarian cancer syndrome (Santarosa M et al. Int. J. Cancer. 1999 Sep;83:5-9; Miolo G et al. BMC Cancer. 2006 Jun;6:156; Manoukian S et al. Eur. J. Cancer 2007 Feb;43:601-6; Papi L et al. Breast Cancer Res. Treat. 2009 Oct;117:497-504; Alemar B et al. Cancer Genet. 2016 Sep;209:417-422). 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, SCV000684004.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

This variant changes 1 nucleotide in exon 22 of the BRCA2 gene, creating a premature translation stop signal. This variant is also known as 9106C>T in the literature. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in more than 10 individuals affected with breast or ovarian cancer (PMID: 16982466, 17224268, 23165508, 28091860, 30606148, 32438681, 33471991, 35281878) and has been identified in 38 families among the CIMBA participants (PMID: 29446198). 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 3, 2024

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