rs757640443
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_001161403.3(LIMS2):c.256C>T(p.Arg86Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R86H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001161403.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LIMS2 | NM_001161403.3 | c.256C>T | p.Arg86Cys | missense_variant | 4/10 | ENST00000355119.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LIMS2 | ENST00000355119.9 | c.256C>T | p.Arg86Cys | missense_variant | 4/10 | 1 | NM_001161403.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152174Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251390Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135874
GnomAD4 exome AF: 0.0000260 AC: 38AN: 1461808Hom.: 0 Cov.: 33 AF XY: 0.0000275 AC XY: 20AN XY: 727210
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74342
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2W Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 27, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 10, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 108 of the LIMS2 protein (p.Arg108Cys). This variant is present in population databases (rs757640443, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with LIMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 574732). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LIMS2 protein function. 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