chr2-70215379-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_022173.4(TIA1):c.880G>A(p.Val294Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,613,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_022173.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152132Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251268Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135816
GnomAD4 exome AF: 0.000182 AC: 266AN: 1461634Hom.: 0 Cov.: 30 AF XY: 0.000164 AC XY: 119AN XY: 727120
GnomAD4 genome AF: 0.000131 AC: 20AN: 152250Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74444
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 20, 2024 | In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29216908, 28817800) - |
Welander distal myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 11, 2024 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 294 of the TIA1 protein (p.Val294Met). This variant is present in population databases (rs144296151, gnomAD 0.01%). This missense change has been observed in individual(s) with amyotrophic lateral sclerosis (ALS) (PMID: 28817800). ClinVar contains an entry for this variant (Variation ID: 575375). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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