NM_000059.4(BRCA2):c.2998A>C (p.Ile1000Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely benign (2 submissions)
Last evaluated:: Jan 2, 2024
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:: RCV002440559.6

Allele description [Variation Report for NM_000059.4(BRCA2):c.2998A>C (p.Ile1000Leu)]

NM_000059.4(BRCA2):c.2998A>C (p.Ile1000Leu)

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.2998A>C (p.Ile1000Leu)

HGVS:

NC_000013.11:g.32337353A>C
NG_012772.3:g.26874A>C
NM_000059.4:c.2998A>CMANE SELECT
NP_000050.2:p.Ile1000Leu
NP_000050.3:p.Ile1000Leu
LRG_293t1:c.2998A>C
LRG_293:g.26874A>C
LRG_293p1:p.Ile1000Leu
NC_000013.10:g.32911490A>C
NM_000059.3:c.2998A>C

Protein change:

I1000L

Links:

dbSNP: rs1555282999

NCBI 1000 Genomes Browser:

rs1555282999

Molecular consequence:

NM_000059.4:c.2998A>C - 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
SCV002750731	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Jan 2, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 33067490, 35264596, 36413997 Citation Link,
SCV003850300	University of Washington Department of Laboratory Medicine, University of Washington	criteria provided, single submitter (Dines et al. (Genet Med. 2020))	Likely benign (Mar 23, 2023)	germline	curation	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002750731

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Jan 2, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV003850300

University of Washington Department of Laboratory Medicine, University of Washington

criteria provided, single submitter

(Dines et al. (Genet Med. 2020))

Likely benign
(Mar 23, 2023)

germline

curation

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

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

BRCA1 and BRCA2 genes mutations among high risk breast cancer patients in Jordan.

Abu-Helalah M, Azab B, Mubaidin R, Ali D, Jafar H, Alshraideh H, Drou N, Awidi A.

Sci Rep. 2020 Oct 16;10(1):17573. doi: 10.1038/s41598-020-74250-2.

PubMed [citation]

PMID:: 33067490
PMCID:: PMC7568559

Detection of germline variants in Brazilian breast cancer patients using multigene panel testing.

Guindalini RSC, Viana DV, Kitajima JPFW, Rocha VM, López RVM, Zheng Y, Freitas É, Monteiro FPM, Valim A, Schlesinger D, Kok F, Olopade OI, Folgueira MAAK.

Sci Rep. 2022 Mar 9;12(1):4190. doi: 10.1038/s41598-022-07383-1.

PubMed [citation]

PMID:: 35264596
PMCID:: PMC8907244

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002750731.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

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 University of Washington Department of Laboratory Medicine, University of Washington, SCV003850300.1

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

Description

Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).

#	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 29, 2024

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