13-32340294-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000059.4(BRCA2):c.5939C>T(p.Thr1980Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1980P) has been classified as Uncertain significance.
Frequency
Consequence
NM_000059.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRCA2 | NM_000059.4 | c.5939C>T | p.Thr1980Ile | missense_variant | 11/27 | ENST00000380152.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRCA2 | ENST00000380152.8 | c.5939C>T | p.Thr1980Ile | missense_variant | 11/27 | 5 | NM_000059.4 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250694Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135756
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461696Hom.: 0 Cov.: 46 AF XY: 0.00 AC XY: 0AN XY: 727150
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 06, 2022 | The p.T1980I variant (also known as c.5939C>T), located in coding exon 10 of the BRCA2 gene, results from a C to T substitution at nucleotide position 5939. The threonine at codon 1980 is replaced by isoleucine, an amino acid with similar properties. This alteration has been reported in an Algerian woman diagnosed with breast cancer at age 40 and no family history of cancer (Henouda S et al. Dis. Markers, 2016 Feb;2016:7869095). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Feb 26, 2019 | - - |
Likely benign, criteria provided, single submitter | curation | University of Washington Department of Laboratory Medicine, University of Washington | Mar 23, 2023 | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). - |
Breast-ovarian cancer, familial, susceptibility to, 2 Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Breast Cancer Information Core (BIC) (BRCA2) | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jun 06, 2023 | A variant of uncertain significant was detected . This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1980 of the BRCA2 protein (p.Thr1980Ile). This variant is present in population databases (rs80358827, gnomAD 0.007%). This missense change has been observed in individual(s) with breast cancer (PMID: 12491487, 26997744). ClinVar contains an entry for this variant (Variation ID: 51966). This amino acid position is highly conserved . In addition, this alteration is predicted to be deleterious and diseases causing by(PolyPhen, BayesDel_addAF, DANN, EIGEN, FATHMMMKL, M-CAP, MVP, MutationTaster and SIFT) . In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Hereditary breast ovarian cancer syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 13, 2023 | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1980 of the BRCA2 protein (p.Thr1980Ile). This variant is present in population databases (rs80358827, gnomAD 0.007%). This missense change has been observed in individual(s) with breast cancer (PMID: 12491487, 26997744). ClinVar contains an entry for this variant (Variation ID: 51966). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BRCA2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at