NM_000059.4(BRCA2):c.9875C>T (p.Pro3292Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Dec 13, 2021
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:: RCV000131346.21

Allele description [Variation Report for NM_000059.4(BRCA2):c.9875C>T (p.Pro3292Leu)]

NM_000059.4(BRCA2):c.9875C>T (p.Pro3292Leu)

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.9875C>T (p.Pro3292Leu)

Other names:

p.P3292L:CCG>CTG; NP_000050.3:p.Pro3292Leu

HGVS:

NC_000013.11:g.32398388C>T
NG_012772.3:g.87909C>T
NM_000059.4:c.9875C>TMANE SELECT
NP_000050.2:p.Pro3292Leu
NP_000050.3:p.Pro3292Leu
LRG_293t1:c.9875C>T
LRG_293:g.87909C>T
LRG_293p1:p.Pro3292Leu
NC_000013.10:g.32972525C>T
NM_000059.3:c.9875C>T
NM_000059.4:c.9875C>T
U43746.1:n.10103C>T
p.P3292L

Nucleotide change:

10103C>T

Protein change:

P3292L

Links:

dbSNP: rs56121817

NCBI 1000 Genomes Browser:

rs56121817

Molecular consequence:

NM_000059.4:c.9875C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000186321	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Benign (Mar 4, 2021)	germline	clinical testing	PubMed (15) [See all records that cite these PMIDs] 15800615, 18593900, 19540122, 20104584, 21520273, 24323938, 24372583, 26577449, 26740942, 27907908, 28477318, 28814288, 29126202, 29802286, 30400234 Citation Link,
SCV000902771	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (May 30, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002532067	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Dec 13, 2021)	germline	curation	PubMed (13) [See all records that cite these PMIDs] 20104584, 21520273, 24372583, 26577449, 27907908, 29802286, 30400234, 33471991, 30287823, 26740942, 32906206, 23704879, 18593900 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000186321

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Benign
(Mar 4, 2021)

germline

clinical testing

PubMed (15)
[See all records that cite these PMIDs]

Citation Link,

SCV000902771

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign
(May 30, 2016)

germline

clinical testing

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

SCV002532067

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Dec 13, 2021)

germline

curation

PubMed (13)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, curation

Citations

PubMed

CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repair.

Esashi F, Christ N, Gannon J, Liu Y, Hunt T, Jasin M, West SC.

Nature. 2005 Mar 31;434(7033):598-604.

PubMed [citation]

PMID:: 15800615

The carboxyl terminus of Brca2 links the disassembly of Rad51 complexes to mitotic entry.

Ayoub N, Rajendra E, Su X, Jeyasekharan AD, Mahen R, Venkitaraman AR.

Curr Biol. 2009 Jul 14;19(13):1075-85. doi: 10.1016/j.cub.2009.05.057. Epub 2009 Jun 18.

PubMed [citation]

PMID:: 19540122
PMCID:: PMC2719694

See all PubMed Citations (20)

Details of each submission

From Ambry Genetics, SCV000186321.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (15)

Description

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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 Color Diagnostics, LLC DBA Color Health, SCV000902771.1

#	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 Sema4, Sema4, SCV002532067.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (13)

#	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: Nov 3, 2024

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