NM_000059.4(BRCA2):c.91T>G (p.Trp31Gly) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 18, 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:: RCV000759687.4

Allele description [Variation Report for NM_000059.4(BRCA2):c.91T>G (p.Trp31Gly)]

NM_000059.4(BRCA2):c.91T>G (p.Trp31Gly)

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.91T>G (p.Trp31Gly)

HGVS:

NC_000013.11:g.32319100T>G
NG_012772.3:g.8621T>G
NG_017006.2:g.1264A>C
NM_000059.4:c.91T>GMANE SELECT
NP_000050.2:p.Trp31Gly
NP_000050.3:p.Trp31Gly
LRG_293t1:c.91T>G
LRG_293:g.8621T>G
LRG_293p1:p.Trp31Gly
NC_000013.10:g.32893237T>G
NM_000059.3:c.91T>G

Protein change:

W31G

Links:

dbSNP: rs80359182

NCBI 1000 Genomes Browser:

rs80359182

Molecular consequence:

NM_000059.4:c.91T>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
SCV000889175	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Jul 12, 2021)	unknown	clinical testing	PubMed (5) [See all records that cite these PMIDs] 31742824, 30410870, 30093976, 19609323, 26467025
SCV005327573	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Oct 18, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000889175

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Jul 12, 2021)

unknown

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV005327573

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Oct 18, 2023)

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

Citations

PubMed

Prevalence of hereditary breast and ovarian cancer (HBOC) predisposition gene mutations among 882 HBOC high-risk Chinese individuals.

Shao D, Cheng S, Guo F, Zhu C, Yuan Y, Hu K, Wang Z, Meng X, Jin X, Xiong Y, Chai X, Li H, Zhang Y, Zhang H, Liu J, Ye M.

Cancer Sci. 2020 Feb;111(2):647-657. doi: 10.1111/cas.14242. Epub 2019 Dec 31.

PubMed [citation]

PMID:: 31742824
PMCID:: PMC7004523

Two Missense Variants Detected in Breast Cancer Probands Preventing BRCA2-PALB2 Protein Interaction.

Caleca L, Catucci I, Figlioli G, De Cecco L, Pesaran T, Ward M, Volorio S, Falanga A, Marchetti M, Iascone M, Tondini C, Zambelli A, Azzollini J, Manoukian S, Radice P, Peterlongo P.

Front Oncol. 2018;8:480. doi: 10.3389/fonc.2018.00480.

PubMed [citation]

PMID:: 30410870
PMCID:: PMC6210650

See all PubMed Citations (5)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000889175.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

#	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, SCV005327573.1

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

Description

Published functional studies demonstrate reduced homology-directed repair activity, sensitivity to PARP inhibitors, disrupted PALB2 binding, and poor cell viability, but retained ability to rescue cell growth (PMID: 30410870, 35979650, 32444794, 37731132); Identified in individuals with breast or ovarian cancer, segregating with disease in one family (PMID: 30410870, 30093976, 32778078); 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 319T>G; This variant is associated with the following publications: (PMID: 30410870, 29884841, 35979650, 9537232, 16793542, 19609323, 18363094, 20215541, 21939546, 22194698, 22678057, 32377563, 24285729, 31586400, 31742824, 30093976, 32778078, 32444794, 37731132)

#	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

Last Updated: Oct 8, 2024

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