NM_000059.4(BRCA2):c.3158T>G (p.Leu1053Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jun 29, 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:: RCV000424640.14

Allele description [Variation Report for NM_000059.4(BRCA2):c.3158T>G (p.Leu1053Ter)]

NM_000059.4(BRCA2):c.3158T>G (p.Leu1053Ter)

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.3158T>G (p.Leu1053Ter)

HGVS:

NC_000013.11:g.32337513T>G
NG_012772.3:g.27034T>G
NM_000059.4:c.3158T>GMANE SELECT
NP_000050.2:p.Leu1053Ter
NP_000050.3:p.Leu1053Ter
LRG_293t1:c.3158T>G
LRG_293:g.27034T>G
LRG_293p1:p.Leu1053Ter
NC_000013.10:g.32911650T>G
NM_000059.3:c.3158T>G
U43746.1:n.3386T>G
p.L1053*

Nucleotide change:

3386T>G

Protein change:

L1053*

Links:

dbSNP: rs41293477

NCBI 1000 Genomes Browser:

rs41293477

Molecular consequence:

NM_000059.4:c.3158T>G - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000517371	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (May 17, 2022)	germline	clinical testing	Citation Link,
SCV001133739	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Jun 29, 2023)	unknown	clinical testing	PubMed (10) [See all records that cite these PMIDs] 21952622, 15131399, 28814288, 29446198, 27356891, 29339979, 23569316, 32853339, 29915322, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000517371

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(May 17, 2022)

germline

clinical testing

Citation Link,

SCV001133739

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Jun 29, 2023)

unknown

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	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

BRCA2 is a moderate penetrance gene contributing to young-onset prostate cancer: implications for genetic testing in prostate cancer patients.

Kote-Jarai Z, Leongamornlert D, Saunders E, Tymrakiewicz M, Castro E, Mahmud N, Guy M, Edwards S, O'Brien L, Sawyer E, Hall A, Wilkinson R, Dadaev T, Goh C, Easton D; UKGPCS Collaborators, Goldgar D, Eeles R.

Br J Cancer. 2011 Oct 11;105(8):1230-4. doi: 10.1038/bjc.2011.383. Epub 2011 Sep 27.

PubMed [citation]

PMID:: 21952622
PMCID:: PMC3208504

Cancer variation associated with the position of the mutation in the BRCA2 gene.

Lubinski J, Phelan CM, Ghadirian P, Lynch HT, Garber J, Weber B, Tung N, Horsman D, Isaacs C, Monteiro AN, Sun P, Narod SA.

Fam Cancer. 2004;3(1):1-10.

PubMed [citation]

PMID:: 15131399

See all PubMed Citations (10)

Details of each submission

From GeneDx, SCV000517371.6

#	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); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Observed in individuals with a personal and/or family history of breast and/or prostate cancer, as well as in unaffected controls (Kote-Jarai 2011, Song 2014, Dobbins 2016, Elimam 2017, Mijuskovic 2018); Also known as 3386T>G; This variant is associated with the following publications: (PMID: 19329713, 29915322, 27356891, 15131399, 21952622, 25525159, 29339979, 29446198, 32853339, 33087929, 21702907, 20002770, 23569316, 27225637, 28814288, 24728189)

#	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, SCV001133739.4

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

Description

The BRCA2 c.3158T>G (p.Leu1053*) variant causes the premature termination of BRCA2 protein synthesis. This variant has been reported in the published literature in an affected individual with breast cancer (PMID: 28814288 (2017)), as well as in individuals with prostate cancer (PMIDs: 32853339 (2021), 29915322 (2018), 23569316 (2013), and 21952622 (2011)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). 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: May 16, 2025

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