rs876659262
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM4
The NM_000465.4(BARD1):c.45_46insCAGCCGAGGATCCGC(p.Gln11_Arg15dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000251 in 1,591,348 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. R15R) has been classified as Likely benign.
Frequency
Consequence
NM_000465.4 inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BARD1 | NM_000465.4 | c.45_46insCAGCCGAGGATCCGC | p.Gln11_Arg15dup | inframe_insertion | 1/11 | ENST00000260947.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BARD1 | ENST00000260947.9 | c.45_46insCAGCCGAGGATCCGC | p.Gln11_Arg15dup | inframe_insertion | 1/11 | 1 | NM_000465.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152168Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000482 AC: 1AN: 207600Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 115096
GnomAD4 exome AF: 6.95e-7 AC: 1AN: 1439180Hom.: 0 Cov.: 74 AF XY: 0.00 AC XY: 0AN XY: 714600
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152168Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74336
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 27, 2022 | The c.31_45dup15 variant (also known as p.Q11_R15dup) is located in coding exon 1 of the BARD1 gene. This variant results from an in-frame duplication of 15 nucleotides at nucleotide positions 31 to 45. This results in the insertion of 5 amino acids (QPRIR) between codons 11 and 15. This amino acid region is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Feb 04, 2019 | - - |
Familial cancer of breast Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | This variant, c.31_45dup, results in the insertion of 5 amino acid(s) of the BARD1 protein (p.Gln11_Arg15dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with BARD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 231609). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 15, 2023 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 23, 2023 | In-frame insertion of five amino acids in a non-repeat region; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at