NM_000059.4(BRCA2):c.2612C>A (p.Ser871Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 2, 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:: RCV003114227.11

Allele description [Variation Report for NM_000059.4(BRCA2):c.2612C>A (p.Ser871Ter)]

NM_000059.4(BRCA2):c.2612C>A (p.Ser871Ter)

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.2612C>A (p.Ser871Ter)

HGVS:

NC_000013.11:g.32336967C>A
NG_012772.3:g.26488C>A
NM_000059.4:c.2612C>AMANE SELECT
NP_000050.2:p.Ser871Ter
NP_000050.3:p.Ser871Ter
LRG_293t1:c.2612C>A
LRG_293:g.26488C>A
LRG_293p1:p.Ser871Ter
NC_000013.10:g.32911104C>A
NM_000059.3:c.2612C>A

Nucleotide change:

2840C>A

Protein change:

S871*

Links:

dbSNP: rs397507634

NCBI 1000 Genomes Browser:

rs397507634

Molecular consequence:

NM_000059.4:c.2612C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Homo sapiens ankyrin repeat and sterile alpha motif domain containing 4B (ANKS4B...
Homo sapiens ankyrin repeat and sterile alpha motif domain containing 4B (ANKS4B), mRNA
gi|1519246130|ref|NM_145865.3|

Nucleotide
Borassodendron machadonis
Borassodendron machadonis
Borassodendron machadonis RefSeq Genome

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003798762	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Aug 2, 2022)	germline	clinical testing	Citation Link,
SCV004219551	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Jan 7, 2022)	unknown	clinical testing	PubMed (9) [See all records that cite these PMIDs] 22762150, 21120943, 20858050, 29084914, 28993434, 29446198, 30720243, 32341426, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003798762

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Aug 2, 2022)

germline

clinical testing

Citation Link,

SCV004219551

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Jan 7, 2022)

unknown

clinical testing

PubMed (9)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1 and BRCA2 mutations carrier cohort (GENEPSO).

Lecarpentier J, Noguès C, Mouret-Fourme E, Gauthier-Villars M, Lasset C, Fricker JP, Caron O, Stoppa-Lyonnet D, Berthet P, Faivre L, Bonadona V, Buecher B, Coupier I, Gladieff L, Gesta P, Eisinger F, Frénay M, Luporsi E, Lortholary A, Colas C, Dugast C, Longy M, et al.

Breast Cancer Res. 2012 Jul 3;14(4):R99. doi: 10.1186/bcr3218.

PubMed [citation]

PMID:: 22762150
PMCID:: PMC3680948

EMMA, a cost- and time-effective diagnostic method for simultaneous detection of point mutations and large-scale genomic rearrangements: application to BRCA1 and BRCA2 in 1,525 patients.

Caux-Moncoutier V, Castéra L, Tirapo C, Michaux D, Rémon MA, Laugé A, Rouleau E, De Pauw A, Buecher B, Gauthier-Villars M, Viovy JL, Stoppa-Lyonnet D, Houdayer C.

Hum Mutat. 2011 Mar;32(3):325-34. doi: 10.1002/humu.21414. Epub 2011 Feb 8.

PubMed [citation]

PMID:: 21120943

See all PubMed Citations (9)

Details of each submission

From GeneDx, SCV003798762.2

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

Description

Nonsense 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; Not observed at significant frequency in large population cohorts (gnomAD); Observed in individuals with breast and/or ovarian cancer (Coulet et al., 2020; Labidi-Galy et al., 2018; De Talhouet et al., 2020); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 2840C>A; This variant is associated with the following publications: (PMID: 25525159, 20858050, 29446198, 32341426, 30720243, 29084914, 34367235, 33858029)

#	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, SCV004219551.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

This nonsense variant causes the premature termination of BRCA2 protein synthesis. The frequency of this variant in the general population, 0.00011 (1/8706 chromosomes, http://gnomad.broadinstitute.org), is consistent with pathogenicity. In the published literature, the variant has been reported in individuals and families with hereditary breast and ovarian cancer (PMIDs: 32341426 (2020), 29084914 (2018), 28993434 (2018), 22762150 (2012), 21120943 (2011), 20858050 (2010)). 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

Last Updated: Nov 3, 2024

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