NM_000059.4(BRCA2):c.9728C>T (p.Pro3243Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Nov 26, 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:: RCV000166251.10

Allele description [Variation Report for NM_000059.4(BRCA2):c.9728C>T (p.Pro3243Leu)]

NM_000059.4(BRCA2):c.9728C>T (p.Pro3243Leu)

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.9728C>T (p.Pro3243Leu)

Other names:

p.P3243L:CCT>CTT

HGVS:

NC_000013.11:g.32398241C>T
NG_012772.3:g.87762C>T
NM_000059.4:c.9728C>TMANE SELECT
NP_000050.2:p.Pro3243Leu
NP_000050.3:p.Pro3243Leu
LRG_293t1:c.9728C>T
LRG_293:g.87762C>T
LRG_293p1:p.Pro3243Leu
NC_000013.10:g.32972378C>T
NM_000059.3:c.9728C>T
U43746.1:n.9956C>T
p.P3243L

Nucleotide change:

9956C>T

Protein change:

P3243L

Links:

dbSNP: rs80359241

NCBI 1000 Genomes Browser:

rs80359241

Molecular consequence:

NM_000059.4:c.9728C>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

Recent activity

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cytochrome c oxidase subunit 1, partial (mitochondrion) [Lumbricillus arenarius]
cytochrome c oxidase subunit 1, partial (mitochondrion) [Lumbricillus arenarius]
gi|1018195065|gb|AMY27677.1|

Protein
Polygalacturonase (plasmid) [Sinorhizobium fredii CCBAU 25509]
Polygalacturonase (plasmid) [Sinorhizobium fredii CCBAU 25509]
gi|1393623015|gnl|A0X55|SF25509_b61 b|AWM28899.1|

Protein
Homo sapiens mRNA for tyrosine phosphatase
Homo sapiens mRNA for tyrosine phosphatase
gi|3929753|emb|X82676.1|

Nucleotide
PD885_RS17075 [Xanthomonas fragariae]
PD885_RS17075 [Xanthomonas fragariae]
Gene ID:61895712

Gene
FGSG_11011 [Fusarium graminearum PH-1]
FGSG_11011 [Fusarium graminearum PH-1]
Gene ID:23557883

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000217031	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Jun 20, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000902988	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Apr 3, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002532056	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Nov 26, 2021)	germline	curation	PubMed (2) [See all records that cite these PMIDs] 31742824, 33471991 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000217031

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Jun 20, 2018)

germline

clinical testing

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

Citation Link,

SCV000902988

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Apr 3, 2017)

germline

clinical testing

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

SCV002532056

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Nov 26, 2021)

germline

curation

PubMed (2)
[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

Detection of BRCA1 and BRCA2 mutations in a selected Hawaii population.

Carney ME, Basiliere MS, Mates K, Sing CK.

Hawaii Med J. 2010 Nov;69(11):268-71.

PubMed [citation]

PMID:: 21218378
PMCID:: PMC3071188

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

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV000217031.6

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

Description

This alteration is classified as likely 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, SCV000902988.1

#	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, SCV002532056.1

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

#	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 16, 2024

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