chr13-32371057-AGCC-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_000059.4(BRCA2):βc.8590_8592delβ(p.Ala2864del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ). Synonymous variant affecting the same amino acid position (i.e. A2864A) has been classified as Likely benign.
Frequency
Consequence
NM_000059.4 inframe_deletion
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.8590_8592del | p.Ala2864del | inframe_deletion | 20/27 | ENST00000380152.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRCA2 | ENST00000380152.8 | c.8590_8592del | p.Ala2864del | inframe_deletion | 20/27 | 5 | NM_000059.4 | A2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461814Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727206
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Apr 15, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 15, 2024 | The c.8590_8592delGCC variant (also known as p.A2864del) is located in coding exon 19 of the BRCA2 gene. This variant results from an in-frame deletion of 3 nucleotides at positions 8590 to 8592. This results in the in-frame deletion of an alanine residue at codon 2864. This variant was detected in 0/143 with breast cancer and 1/382 with ovarian cancer from Peru (Ferreyra Y et al. Front Oncol, 2023 Aug;13:1227864). This amino acid position is not well conserved in available vertebrate species. Based on the available evidence, the clinical significance of this variant remains unclear. - |
Hereditary breast ovarian cancer syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 20, 2023 | This variant is not present in population databases (gnomAD no frequency). 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 462485). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant, c.8590_8592del, results in the deletion of 1 amino acid(s) of the BRCA2 protein (p.Ala2864del), but otherwise preserves the integrity of the reading frame. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at