NM_000059.4(BRCA2):c.2274T>G (p.Ser758Arg) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 27, 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:: RCV000589431.13

Allele description [Variation Report for NM_000059.4(BRCA2):c.2274T>G (p.Ser758Arg)]

NM_000059.4(BRCA2):c.2274T>G (p.Ser758Arg)

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.2274T>G (p.Ser758Arg)

Other names:

p.S758R:AGT>AGG

HGVS:

NC_000013.11:g.32336629T>G
NG_012772.3:g.26150T>G
NM_000059.4:c.2274T>GMANE SELECT
NP_000050.2:p.Ser758Arg
NP_000050.3:p.Ser758Arg
LRG_293t1:c.2274T>G
LRG_293:g.26150T>G
LRG_293p1:p.Ser758Arg
NC_000013.10:g.32910766T>G
NM_000059.3:c.2274T>G
p.S758R

Protein change:

S758R

Links:

dbSNP: rs142243359

NCBI 1000 Genomes Browser:

rs142243359

Molecular consequence:

NM_000059.4:c.2274T>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000210286	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Sep 27, 2024)	germline	clinical testing	Citation Link,
SCV001133705	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Jun 2, 2023)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 35264596, 27741520, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000210286

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Sep 27, 2024)

germline

clinical testing

Citation Link,

SCV001133705

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Jun 2, 2023)

unknown

clinical testing

PubMed (3)
[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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Detection of germline variants in Brazilian breast cancer patients using multigene panel testing.

Guindalini RSC, Viana DV, Kitajima JPFW, Rocha VM, López RVM, Zheng Y, Freitas É, Monteiro FPM, Valim A, Schlesinger D, Kok F, Olopade OI, Folgueira MAAK.

Sci Rep. 2022 Mar 9;12(1):4190. doi: 10.1038/s41598-022-07383-1.

PubMed [citation]

PMID:: 35264596
PMCID:: PMC8907244

Prevalence of BRCA1/BRCA2 mutations in a Brazilian population sample at-risk for hereditary breast cancer and characterization of its genetic ancestry.

Fernandes GC, Michelli RA, Galvão HC, Paula AE, Pereira R, Andrade CE, Felicio PS, Souza CP, Mendes DR, Volc S, Berardinelli GN, Grasel RS, Sabato CS, Viana DV, Mauad EC, Scapulatempo-Neto C, Arun B, Reis RM, Palmero EI.

Oncotarget. 2016 Dec 6;7(49):80465-80481. doi: 10.18632/oncotarget.12610.

PubMed [citation]

PMID:: 27741520
PMCID:: PMC5348334

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000210286.20

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

Description

Observed in individuals with breast or ovarian cancer (PMID: 27741520, 37664050, 35264596); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as 2502T>G; This variant is associated with the following publications: (PMID: 29884841, 31911673, 32377563, 35264596, 27741520, 37664050)

#	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, SCV001133705.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

In the published literature, this variant has been reported in individuals with breast cancer (PMID: 35264596 (2022), 27741520 (2016)). The frequency of this variant in the general population, 0.00036 (9/24956 chromosomes in African/African American subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. 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

Last Updated: Oct 8, 2024

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