NM_000059.4(BRCA2):c.6560C>T (p.Pro2187Leu) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Apr 28, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV000589601.24

Allele description [Variation Report for NM_000059.4(BRCA2):c.6560C>T (p.Pro2187Leu)]

NM_000059.4(BRCA2):c.6560C>T (p.Pro2187Leu)

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.6560C>T (p.Pro2187Leu)

Other names:

p.P2187L:CCT>CTT

HGVS:

NC_000013.11:g.32340915C>T
NG_012772.3:g.30436C>T
NM_000059.4:c.6560C>TMANE SELECT
NP_000050.2:p.Pro2187Leu
NP_000050.3:p.Pro2187Leu
LRG_293t1:c.6560C>T
LRG_293:g.30436C>T
LRG_293p1:p.Pro2187Leu
NC_000013.10:g.32915052C>T
NM_000059.3:c.6560C>T
U43746.1:n.6788C>T
p.P2187L

Nucleotide change:

6788C>T

Protein change:

P2187L

Links:

dbSNP: rs56019712

NCBI 1000 Genomes Browser:

rs56019712

Molecular consequence:

NM_000059.4:c.6560C>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
SCV000210631	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (Jun 14, 2021)	germline	clinical testing	Citation Link,
SCV000600712	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Likely benign (Apr 28, 2022)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 34196900, 26467025
SCV002049876	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2021)	Uncertain significance (Jan 10, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000210631

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely benign
(Jun 14, 2021)

germline

clinical testing

Citation Link,

SCV000600712

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Likely benign
(Apr 28, 2022)

unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV002049876

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2021)

Uncertain significance
(Jan 10, 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	unknown	unknown	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

Germline variants in hereditary breast cancer genes are associated with early age at diagnosis and family history in Guatemalan breast cancer.

Ren M, Orozco A, Shao K, Albanez A, Ortiz J, Cao B, Wang L, Barreda L, Alvarez CS, Garland L, Wu D, Chung CC, Wang J, Frone M, Ralon S, Argueta V, Orozco R, Gharzouzi E, Dean M.

Breast Cancer Res Treat. 2021 Sep;189(2):533-539. doi: 10.1007/s10549-021-06305-5. Epub 2021 Jul 1. Erratum in: Breast Cancer Res Treat. 2022 Jan;191(1):227. doi: 10.1007/s10549-021-06373-7.

PubMed [citation]

PMID:: 34196900
PMCID:: PMC8357728

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From GeneDx, SCV000210631.13

#	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 associated with the following publications: (PMID: 24651015)

#	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, SCV000600712.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

#	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 ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV002049876.3

#	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.6560C>T; p.Pro2187Leu variant (rs56019712), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 38052). This variant is found in the Latino population with an overall allele frequency of 0.08% (29/34630 alleles) in the Genome Aggregation Database. The proline at codon 2187 is moderately conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.336). Given the lack of clinical and functional data, the significance of the p.Pro2187Leu 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: Oct 20, 2024

ClinVar

Relating variation to medicine