13-32329430-T-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_000059.4(BRCA2):c.632-13T>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000028 in 1,429,694 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000059.4 splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRCA2 | NM_000059.4 | c.632-13T>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000380152.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRCA2 | ENST00000380152.8 | c.632-13T>G | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_000059.4 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000280 AC: 4AN: 1429694Hom.: 0 Cov.: 27 AF XY: 0.00000281 AC XY: 2AN XY: 712172
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 28, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 22, 2016 | Variant summary: The c.632-13T>G variant affects a non-conserved intronic nucleotide. One in-silico tool predicts damaging outcome for this variant. 5/5 splice-tools in Alamut predict that this variant does not affect normal splicing. This variant is not found in 90320 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical laboratories; nor evaluated for functional impact by in vivo/vitro studies. Considering all evidence, the variant was classified as a VUS-possibly benign until more information becomes available. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 21, 2015 | This variant is denoted BRCA2 c.632-13T>G or IVS7-13T>G and consists of a T>G nucleotide substitution at the -13 position of intron 7 of the BRCA2 gene. Multiple in silico models predict this variant to weaken the nearby natural acceptor site, and to possibly cause abnormal gene splicing; however, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 c.632-13T>G was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. The thymine (T) nucleotide that is altered is conserved in mammals. Based on currently available information, it is unclear whether BRCA2 c.632-13T>G is pathogenic or benign. We consider it to be a variant of uncertain significance. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jun 11, 2019 | - - |
Breast-ovarian cancer, familial, susceptibility to, 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | May 23, 2018 | - - |
Hereditary breast ovarian cancer syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at