NM_000059.4(BRCA2):c.2810A>C (p.Gln937Pro) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 24, 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:: RCV000160050.4

Allele description [Variation Report for NM_000059.4(BRCA2):c.2810A>C (p.Gln937Pro)]

NM_000059.4(BRCA2):c.2810A>C (p.Gln937Pro)

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.2810A>C (p.Gln937Pro)

Other names:

p.Q937P:CAA>CCA

HGVS:

NC_000013.11:g.32337165A>C
NG_012772.3:g.26686A>C
NM_000059.4:c.2810A>CMANE SELECT
NP_000050.2:p.Gln937Pro
NP_000050.3:p.Gln937Pro
LRG_293t1:c.2810A>C
LRG_293:g.26686A>C
LRG_293p1:p.Gln937Pro
NC_000013.10:g.32911302A>C
NM_000059.3:c.2810A>C

Protein change:

Q937P

Links:

dbSNP: rs730881516

NCBI 1000 Genomes Browser:

rs730881516

Molecular consequence:

NM_000059.4:c.2810A>C - 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
SCV000210292	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Jun 13, 2017)	germline	clinical testing	Citation Link,
SCV003799464	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2021)	Uncertain significance (Mar 24, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000210292

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Jun 13, 2017)

germline

clinical testing

Citation Link,

SCV003799464

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2021)

Uncertain significance
(Mar 24, 2022)

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	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000210292.12

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

Description

This variant is denoted BRCA2 c.2810A>C at the cDNA level, p.Gln937Pro (Q937P) at the protein level, and results in the change of a Glutamine to a Proline (CAA>CCA). Using alternate nomenclature, this variant would be defined as BRCA2 3038A>C. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Gln937Pro was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Glutamine and Proline differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Gln937Pro occurs at a position that is not conserved and is not located in a known functional domain. In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRCA2 Gln937Pro is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

#	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 ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV003799464.2

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

Description

The BRCA2 c.2810A>C; p.Gln937Pro variant (rs730881516), to our knowledge, is not reported in the medical literature in individuals with hereditary breast and ovarian cancer syndrome but is reported in ClinVar (Variation ID: 182191). This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. The glutamine at codon 937 is moderately conserved but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.319). Due to limited information, the clinical significance of this variant is uncertain at this time.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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