NM_000059.4(BRCA2):c.7916C>T (p.Pro2639Leu) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Apr 14, 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:: RCV000679188.10

Allele description [Variation Report for NM_000059.4(BRCA2):c.7916C>T (p.Pro2639Leu)]

NM_000059.4(BRCA2):c.7916C>T (p.Pro2639Leu)

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.7916C>T (p.Pro2639Leu)

HGVS:

NC_000013.11:g.32362633C>T
NG_012772.3:g.52154C>T
NM_000059.4:c.7916C>TMANE SELECT
NP_000050.2:p.Pro2639Leu
NP_000050.3:p.Pro2639Leu
LRG_293t1:c.7916C>T
LRG_293:g.52154C>T
LRG_293p1:p.Pro2639Leu
NC_000013.10:g.32936770C>T
NM_000059.3:c.7916C>T

Nucleotide change:

8144C>T

Protein change:

P2639L

Links:

dbSNP: rs774723315

NCBI 1000 Genomes Browser:

rs774723315

Molecular consequence:

NM_000059.4:c.7916C>T - 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
SCV000805770	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 12, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000889138	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Jun 27, 2021)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 29335924, 27376475, 29884841, 26467025
SCV003918460	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Apr 14, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000805770

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 12, 2017)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV000889138

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Jun 27, 2021)

unknown

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV003918460

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Apr 14, 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	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
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

BRCA1 and BRCA2 germline variants in breast cancer patients from the Republic of Macedonia.

Jakimovska M, Maleva Kostovska I, Popovska-Jankovic K, Kubelka-Sabit K, Karadjozov M, Stojanovska L, Arsovski A, Smichkoska S, Lazarova E, Jakimovska Dimitrovska M, Plaseska-Karanfilska D.

Breast Cancer Res Treat. 2018 Apr;168(3):745-753. doi: 10.1007/s10549-017-4642-5. Epub 2018 Jan 15.

PubMed [citation]

PMID:: 29335924

See all PubMed Citations (5)

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV000805770.1

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000889138.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

#	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, SCV003918460.1

#	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 no damaging effect: no impact on homology-directed repair (HDR) activity (Hart et al., 2019; Richardson et al., 2021; Iversen et al., 2022); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in an individual with personal and family history of breast cancer (Jakimovska et al., 2018); Not observed at significant frequency in large population cohorts (gnomAD); Also known as 8144C>T; This variant is associated with the following publications: (PMID: 32444794, 33609447, 29884841, 29335924, 35665744, 12228710)

#	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: Sep 29, 2024

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