NM_000059.4(BRCA2):c.3515C>G (p.Ser1172Trp) AND not provided

Germline classification:: Uncertain significance (4 submissions)
Last evaluated:: Jul 1, 2024
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:: RCV000985504.7

Allele description [Variation Report for NM_000059.4(BRCA2):c.3515C>G (p.Ser1172Trp)]

NM_000059.4(BRCA2):c.3515C>G (p.Ser1172Trp)

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.3515C>G (p.Ser1172Trp)

HGVS:

NC_000013.11:g.32337870C>G
NG_012772.3:g.27391C>G
NM_000059.4:c.3515C>GMANE SELECT
NP_000050.2:p.Ser1172Trp
NP_000050.3:p.Ser1172Trp
LRG_293t1:c.3515C>G
LRG_293:g.27391C>G
LRG_293p1:p.Ser1172Trp
NC_000013.10:g.32912007C>G
NM_000059.3:c.3515C>G
U43746.1:n.3743C>G

Nucleotide change:

3743C>G

Protein change:

S1172W

Links:

dbSNP: rs80358600

NCBI 1000 Genomes Browser:

rs80358600

Molecular consequence:

NM_000059.4:c.3515C>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001133760	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Jun 2, 2023)	unknown	clinical testing	PubMed (6) [See all records that cite these PMIDs] 25896959, 32772980, 33471991, 31911673, 32377563, 26467025
SCV004039681	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Sep 27, 2023)	germline	clinical testing	Citation Link,
SCV005199781	Clinical Genetics Laboratory, Skane University Hospital Lund	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 15, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005329984	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Jul 1, 2024)	germline	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	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

The molecular analysis of BRCA1 and BRCA2: Next-generation sequencing supersedes conventional approaches.

D'Argenio V, Esposito MV, Telese A, Precone V, Starnone F, Nunziato M, Cantiello P, Iorio M, Evangelista E, D'Aiuto M, Calabrese A, Frisso G, D'Aiuto G, Salvatore F.

Clin Chim Acta. 2015 Jun 15;446:221-5. doi: 10.1016/j.cca.2015.03.045. Epub 2015 Apr 17.

PubMed [citation]

PMID:: 25896959

Genetic testing in Poland and Ukraine: should comprehensive germline testing of BRCA1 and BRCA2 be recommended for women with breast and ovarian cancer?

Nguyen-Dumont T, Karpinski P, Sasiadek MM, Akopyan H, Steen JA, Theys D, Hammet F, Tsimiklis H, Park DJ, Pope BJ, Slezak R, Stembalska A, Pesz K, Kitsera N, Siekierzynska A, Southey MC, Myszka A.

Genet Res (Camb). 2020 Aug 10;102:e6. doi: 10.1017/S0016672320000075.

PubMed [citation]

PMID:: 32772980
PMCID:: PMC7443769

See all PubMed Citations (7)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001133760.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

In the published literature, the variant has been reported in individuals with breast and/or ovarian cancer (PMIDs: 33471991 (2021), 32772980 (2020), and 25896959 (2015)). This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

#	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

From GeneDx, SCV004039681.1

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as 3743C>G; This variant is associated with the following publications: (PMID: 25896959, 32772980, 24817641, 29884841, 32377563, 31131967, 25682074, 33471991, 35263119, 31853058)

#	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 Clinical Genetics Laboratory, Skane University Hospital Lund, SCV005199781.1

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

#	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 CeGaT Center for Human Genetics Tuebingen, SCV005329984.2

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

Description

BRCA2: PM2, BP4

#	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		1	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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