rs397507919
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000059.4(BRCA2):c.7538delC(p.Ala2513GlufsTer11) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000059.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BRCA2 | ENST00000380152.8 | c.7538delC | p.Ala2513GlufsTer11 | frameshift_variant | Exon 15 of 27 | 5 | NM_000059.4 | ENSP00000369497.3 | ||
BRCA2 | ENST00000530893.7 | c.7169delC | p.Ala2390GlufsTer11 | frameshift_variant | Exon 15 of 27 | 1 | ENSP00000499438.2 | |||
BRCA2 | ENST00000614259.2 | n.7538delC | non_coding_transcript_exon_variant | Exon 14 of 26 | 2 | ENSP00000506251.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Breast-ovarian cancer, familial, susceptibility to, 2 Pathogenic:2
Variant allele predicted to encode a truncated non-functional protein. -
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Hereditary cancer-predisposing syndrome Pathogenic:1
The c.7538delC pathogenic mutation, located in coding exon 14 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 7538, causing a translational frameshift with a predicted alternate stop codon (p.A2513Efs*11). This alteration has been reported in one patient from a Korean breast and ovarian cancer cohort (Kim H et al. Breast Cancer Res. Treat., 2012 Aug;134:1315-26). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at