rs761054820
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_012208.4(HARS2):c.502C>T(p.Arg168Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_012208.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152126Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251494Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135922
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461888Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 727244
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152126Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74298
ClinVar
Submissions by phenotype
not specified Uncertain:1
The p.Arg168Cys variant in HARS2 has not been previously reported in individuals with hearing loss or Perrault syndrome, but has been identified in 3/66740 of E uropean chromosomes and 1/10406 of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs761054820). Although t his variant has been seen in the general population, its frequency is not high e nough to rule out a pathogenic role. Computational prediction tools and conserva tion analysis suggest that the p.Arg168Cys variant may impact the protein, thoug h this information is not predictive enough to determine pathogenicity. In summa ry, the clinical significance of the p.Arg168Cys variant is uncertain. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at