rs143214959
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000059.4(BRCA2):c.750G>A(p.Val250=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000831 in 1,613,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★★). Synonymous variant affecting the same amino acid position (i.e. V250V) has been classified as Likely benign.
Frequency
Consequence
NM_000059.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRCA2 | NM_000059.4 | c.750G>A | p.Val250= | synonymous_variant | 9/27 | ENST00000380152.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRCA2 | ENST00000380152.8 | c.750G>A | p.Val250= | synonymous_variant | 9/27 | 5 | NM_000059.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000399 AC: 10AN: 250922Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135654
GnomAD4 exome AF: 0.0000869 AC: 127AN: 1461282Hom.: 0 Cov.: 30 AF XY: 0.0000867 AC XY: 63AN XY: 726968
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74302
ClinVar
Submissions by phenotype
Breast-ovarian cancer, familial, susceptibility to, 2 Benign:6
Likely benign, criteria provided, single submitter | clinical testing | Genetics and Molecular Pathology, SA Pathology | May 18, 2020 | The BRCA2 c.750G>A variant is classified as Likely Benign (BP2, BP6) - |
Benign, no assertion criteria provided | clinical testing | Sharing Clinical Reports Project (SCRP) | Mar 01, 2011 | - - |
Likely benign, no assertion criteria provided | clinical testing | Department of Medical Genetics, University Hospital of North Norway | May 01, 2016 | - - |
Likely benign, reviewed by expert panel | curation | Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) | Jun 29, 2017 | Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/). - |
Likely benign, criteria provided, single submitter | clinical testing | Michigan Medical Genetics Laboratories, University of Michigan | Apr 21, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Nov 20, 2023 | - - |
not specified Benign:4
Likely benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Feb 06, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 23, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 03, 2013 | 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 a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | research | King Laboratory, University of Washington | Sep 01, 2019 | - - |
Hereditary cancer-predisposing syndrome Benign:3
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jun 27, 2016 | - - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Sep 16, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 06, 2014 | 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. - |
BRCA2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 09, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Nov 01, 2022 | - - |
Hereditary breast ovarian cancer syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at