rs80359362
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM4
The NM_000059.4(BRCA2):βc.291_296delβ(p.Glu97_Leu98del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,832 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. K96K) 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 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRCA2 | NM_000059.4 | c.291_296del | p.Glu97_Leu98del | inframe_deletion | 3/27 | ENST00000380152.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRCA2 | ENST00000380152.8 | c.291_296del | p.Glu97_Leu98del | inframe_deletion | 3/27 | 5 | NM_000059.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152248Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461584Hom.: 0 AF XY: 0.00000963 AC XY: 7AN XY: 727100
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74390
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jun 14, 2016 | Variant summary: The BRCA2 c.291_296delATTAGA (p.Glu97_Leu98del) variant results in an in-frame deletion. One in silico tool predicts a disease-causing outcome for this variant. This variant was absent in 120164 control chromosomes, and has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as a VUS. However, this variant has been found to co-occur in one LCA internal specimen with a pathogenic BRCA1 variant, c.4964_4982delCTGGCCTGACCCCAGAAGA, and in one patient reported in the BIC database with a pathogenic BRCA2 variant, c.4131_4132insTGAGGA (p.Thr1378_Gly1712delinsTer) in one individual. Taken together, the variant was classified as a variant of uncertain significance (VUS)-possibly benign until additional information becomes available. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 25, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 24, 2022 | In-frame deletion of 2 amino acids in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; Also known as 519_524del; 519_524delATTAGA - |
Breast-ovarian cancer, familial, susceptibility to, 2 Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Breast Cancer Information Core (BIC) (BRCA2) | Feb 16, 2001 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Sharing Clinical Reports Project (SCRP) | Aug 30, 2011 | - - |
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jun 17, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 08, 2023 | The c.291_296delATTAGA variant (also known as p.E97_L98del) is located in coding exon 2 of the BRCA2 gene. This variant results from an in-frame ATTAGA deletion at nucleotide positions 291 to 296. This results in the in-frame deletion of glutamate and leucine residues at codons 97 and 98. These amino acid positions are not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Familial cancer of breast Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Feb 13, 2024 | - - |
Hereditary breast ovarian cancer syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 27, 2023 | This variant, c.291_296del, results in the deletion of 2 amino acid(s) of the BRCA2 protein (p.Glu97_Leu98del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs80359362, gnomAD 0.007%). This variant has been observed to co-occur in individuals with a different variant in BRCA2 that has been determined to be pathogenic (PMID: 10923033), but the significance of this finding is unclear. ClinVar contains an entry for this variant (Variation ID: 51371). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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