10-125836742-TC-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_018180.3(DHX32):c.2176delG(p.Glu726AsnfsTer57) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,614,092 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_018180.3 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DHX32 | ENST00000284690.4 | c.2176delG | p.Glu726AsnfsTer57 | frameshift_variant | Exon 11 of 11 | 1 | NM_018180.3 | ENSP00000284690.3 | ||
BCCIP | ENST00000278100.11 | c.*469delC | downstream_gene_variant | 1 | NM_078468.3 | ENSP00000278100.6 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251462Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135912
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727242
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74370
ClinVar
Submissions by phenotype
not provided Uncertain:1
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. This sequence change results in a frameshift in the DHX32 gene (p.Glu726Asnfs*57). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 18 amino acid(s) of the DHX32 protein and extend the protein by 38 additional amino acid residues. This variant is present in population databases (rs772571642, gnomAD 0.01%). This frameshift has been observed in individual(s) with inherited retinal disease (PMID: 29320387). ClinVar contains an entry for this variant (Variation ID: 2136941). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at