chr13-32338946-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP6
The NM_000059.4(BRCA2):āc.4591A>Gā(p.Lys1531Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,634 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. K1531N) has been classified as Likely benign.
Frequency
Consequence
NM_000059.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRCA2 | NM_000059.4 | c.4591A>G | p.Lys1531Glu | missense_variant | 11/27 | ENST00000380152.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRCA2 | ENST00000380152.8 | c.4591A>G | p.Lys1531Glu | missense_variant | 11/27 | 5 | NM_000059.4 | A2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461634Hom.: 0 Cov.: 45 AF XY: 0.00 AC XY: 0AN XY: 727112
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
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). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 18, 2021 | The p.K1531E variant (also known as c.4591A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 4591. The lysine at codon 1531 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Breast and/or ovarian cancer Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Aug 30, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at