NM_000059.4(BRCA2):c.2813C>A (p.Ala938Glu) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jul 26, 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:: RCV000587088.12

Allele description [Variation Report for NM_000059.4(BRCA2):c.2813C>A (p.Ala938Glu)]

NM_000059.4(BRCA2):c.2813C>A (p.Ala938Glu)

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.2813C>A (p.Ala938Glu)

HGVS:

NC_000013.11:g.32337168C>A
NG_012772.3:g.26689C>A
NM_000059.4:c.2813C>AMANE SELECT
NP_000050.2:p.Ala938Glu
NP_000050.3:p.Ala938Glu
LRG_293t1:c.2813C>A
LRG_293:g.26689C>A
LRG_293p1:p.Ala938Glu
NC_000013.10:g.32911305C>A
NM_000059.3:c.2813C>A
U43746.1:n.3041C>A
p.A938E

Protein change:

A938E

Links:

dbSNP: rs55773834

NCBI 1000 Genomes Browser:

rs55773834

Molecular consequence:

NM_000059.4:c.2813C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Mus musculus placenta specific 9 (Plac9), mRNA
Mus musculus placenta specific 9 (Plac9), mRNA
gi|2194135900|ref|NM_207229.3|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000278842	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jul 26, 2023)	germline	clinical testing	Citation Link,
SCV000889011	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Mar 3, 2023)	unknown	clinical testing	PubMed (12) [See all records that cite these PMIDs] 26689913, 26295337, 31911673, 32377563, 31853058, 29884841, 30787465, 30311369, 28569743, 28873162, 23929434, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000278842

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jul 26, 2023)

germline

clinical testing

Citation Link,

SCV000889011

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Mar 3, 2023)

unknown

clinical testing

PubMed (12)
[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

Patterns and functional implications of rare germline variants across 12 cancer types.

Lu C, Xie M, Wendl MC, Wang J, McLellan MD, Leiserson MD, Huang KL, Wyczalkowski MA, Jayasinghe R, Banerjee T, Ning J, Tripathi P, Zhang Q, Niu B, Ye K, Schmidt HK, Fulton RS, McMichael JF, Batra P, Kandoth C, Bharadwaj M, Koboldt DC, et al.

Nat Commun. 2015 Dec 22;6:10086. doi: 10.1038/ncomms10086.

PubMed [citation]

PMID:: 26689913
PMCID:: PMC4703835

Development and Validation of a Next-Generation Sequencing Assay for BRCA1 and BRCA2 Variants for the Clinical Laboratory.

Strom CM, Rivera S, Elzinga C, Angeloni T, Rosenthal SH, Goos-Root D, Siaw M, Platt J, Braastadt C, Cheng L, Ross D, Sun W.

PLoS One. 2015;10(8):e0136419. doi: 10.1371/journal.pone.0136419.

PubMed [citation]

PMID:: 26295337
PMCID:: PMC4546651

See all PubMed Citations (12)

Details of each submission

From GeneDx, SCV000278842.13

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in individuals with glioblastoma and breast cancer (Lu et al., 2015; Renata Mendes de Freitas et al., 2022); Also known as 3041C>A; This variant is associated with the following publications: (PMID: 28873162, 23929434, 26689913, 28122867, de Freitas_2022, 32377563, 31911673, 26295337, 29884841, 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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000889011.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (12)

Description

The frequency of this variant in the general population, 0.0004 (10/24886 chromosomes in the African/African American subpopulation, http://gnomad.broadinstitute.org), is higher than would generally be expected for pathogenic variants in this gene. In the published literature, the variant has been reported in individuals affected with breast cancer (Freitas et al. 2022. Mastology 32:e20220003), glioblastoma (PMID: 26689913 (2015)), and an advanced cancer (PMID: 28873162 (2017)). 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 26, 2024

ClinVar

Relating variation to medicine