chr5-140693645-TTTA-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PM4_SupportingBS1_Supporting
The NM_012208.4(HARS2):c.168_170delTAT(p.Ile57del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,613,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_012208.4 disruptive_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251496Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135922
GnomAD4 exome AF: 0.0000397 AC: 58AN: 1461628Hom.: 0 AF XY: 0.0000591 AC XY: 43AN XY: 727134
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152264Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74458
ClinVar
Submissions by phenotype
not specified Uncertain:1
The p.Ile57del variant in HARS2 has not been previously reported in individuals with hearing loss or Perrault syndrome, but has been identified in 4/16512 South Asians chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broad institute.org). This variant is a deletion of 1 amino acid at position 57 and is not predicted to alter the protein reading-frame. However, its impact on the fu nction of the protein cannot be predicted. In summary, the clinical significance of the p.Ile57del variant is uncertain. -
not provided Uncertain:1
In-frame deletion of 1 amino acids in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; 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