chr13-32340619-T-C
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000059.4(BRCA2):c.6264T>C(p.Thr2088=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000299 in 1,607,372 control chromosomes in the GnomAD database, including 2 homozygotes. 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. T2088T) 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.6264T>C | p.Thr2088= | synonymous_variant | 11/27 | ENST00000380152.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRCA2 | ENST00000380152.8 | c.6264T>C | p.Thr2088= | synonymous_variant | 11/27 | 5 | NM_000059.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000612 AC: 15AN: 245016Hom.: 0 AF XY: 0.0000905 AC XY: 12AN XY: 132562
GnomAD4 exome AF: 0.0000323 AC: 47AN: 1455162Hom.: 2 Cov.: 46 AF XY: 0.0000498 AC XY: 36AN XY: 723580
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74364
ClinVar
Submissions by phenotype
Breast-ovarian cancer, familial, susceptibility to, 2 Benign:3
Likely benign, no assertion criteria provided | clinical testing | BRCAlab, Lund University | Mar 02, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Nov 30, 2023 | - - |
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/). - |
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Sep 24, 2020 | - - |
Likely benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The p.Thr2088Thr variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. This variant was identified in the literature by Cvok (2008) in 2 of 115 healthy elderly Croatian women with no family history of cancer. The variant was not identified in any of the databases searched, including dbSNP, UMD, the NHLBI Exome Sequencing Project (Exome Variant Server), HGMD, LOVD, COSMIC, or the BIC database. In silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing; though Cvok (2008) found that an additional program, ESEfinder 3.0, predicted a potential change in splicing motifs. However, these in silico predictions are not very predictive of pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as predicted benign. - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 16, 2020 | This variant is associated with the following publications: (PMID: 18844490, 22366370) - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 15, 2015 | 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jul 22, 2015 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Sep 20, 2019 | - - |
Medulloblastoma;C0346153:Familial cancer of breast;C0376358:Malignant tumor of prostate;C1838457:Fanconi anemia complementation group D1;C2675520:Breast-ovarian cancer, familial, susceptibility to, 2;C2751641:Glioma susceptibility 3;C3150546:Pancreatic cancer, susceptibility to, 2;CN033288:Wilms tumor 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 22, 2022 | - - |
Hereditary breast ovarian cancer syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at