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NM_000059.3(BRCA2):c.2999T>C (p.Ile1000Thr)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(2);Uncertain significance(6)

Review status:
criteria provided, conflicting interpretations
Submissions:
8 (Most recent: Mar 28, 2019)
Last evaluated:
Nov 13, 2018
Accession:
VCV000142073.4
Variation ID:
142073
Description:
single nucleotide variant
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NM_000059.3(BRCA2):c.2999T>C (p.Ile1000Thr)

Allele ID
151787
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
13q13.1
Genomic location
13: 32337354 (GRCh38) GRCh38 UCSC
13: 32911491 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000013.11:g.32337354T>C
NC_000013.10:g.32911491T>C
LRG_293t1:c.2999T>C LRG_293p1:p.Ile1000Thr
... more HGVS
Protein change
I1000T
Other names
p.I1000T:ATT>ACT
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
dbSNP: rs374769365
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter Nov 13, 2018 RCV000257906.6
Uncertain significance 1 criteria provided, single submitter Jun 6, 2016 RCV000587614.1
Uncertain significance 1 criteria provided, single submitter May 17, 2017 RCV000768593.1
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Aug 1, 2016 RCV000130892.5
Conflicting interpretations of pathogenicity 3 criteria provided, conflicting interpretations Sep 21, 2017 RCV000168562.8
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
BRCA2 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
10748 10826

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Jan 22, 2014)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Department of Pathology and Laboratory Medicine,Sinai Health System
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591842.1
Submitted: (Apr 19, 2017)
Evidence details
Uncertain significance
(Mar 06, 2017)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000296680.2
Submitted: (Aug 01, 2017)
Evidence details
Publications
PubMed (1)
Uncertain significance
(Jun 06, 2016)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Integrated Genetics/Laboratory Corporation of America
Accession: SCV000694659.1
Submitted: (Jan 25, 2018)
Evidence details
Comment:
Variant summary: The BRCA2 c.2999T>C (p.Ile1000Thr) variant involves the alteration of a non-conserved nucleotide. 3/5 in silico tools predict a benign outcome. This variant was ... (more)
Likely benign
(Sep 21, 2017)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
GeneDx
Accession: SCV000210300.9
Submitted: (Mar 26, 2018)
Evidence details
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at ... (more)
Uncertain significance
(Aug 01, 2016)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000185801.5
Submitted: (Jul 30, 2018)
Evidence details
Comment:
Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Uncertain significance
(May 17, 2017)
criteria provided, single submitter
Method: clinical testing
Breast and/or ovarian cancer
Allele origin: germline
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario
Study: Canadian Open Genetics Repository
Accession: SCV000219323.4
Submitted: (Apr 30, 2018)
Evidence details
Likely benign
(Nov 17, 2015)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color
Accession: SCV000905819.1
Submitted: (Nov 06, 2018)
Evidence details
Uncertain significance
(Nov 13, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Invitae
Accession: SCV000549689.4
Submitted: (Mar 28, 2019)
Evidence details
Publications
PubMed (1)
Comment:
This sequence change replaces isoleucine with threonine at codon 1000 of the BRCA2 protein (p.Ile1000Thr). The isoleucine residue is weakly conserved and there is a ... (more)

Citations for this variant

Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Development and Validation of a Next-Generation Sequencing Assay for BRCA1 and BRCA2 Variants for the Clinical Laboratory. Strom CM PloS one 2015 PMID: 26295337

Record last updated Oct 11, 2019