rs141505120
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001161403.3(LIMS2):c.619G>A(p.Gly207Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,610,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. G207G) has been classified as Benign.
Frequency
Consequence
NM_001161403.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LIMS2 | NM_001161403.3 | c.619G>A | p.Gly207Ser | missense_variant | 6/10 | ENST00000355119.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LIMS2 | ENST00000355119.9 | c.619G>A | p.Gly207Ser | missense_variant | 6/10 | 1 | NM_001161403.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000164 AC: 25AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000573 AC: 14AN: 244204Hom.: 0 AF XY: 0.0000601 AC XY: 8AN XY: 133110
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1458096Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10AN XY: 725070
GnomAD4 genome ? AF: 0.000164 AC: 25AN: 152338Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74488
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 | May 15, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 03, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 229 of the LIMS2 protein (p.Gly229Ser). This variant is present in population databases (rs141505120, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. 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: 566596). 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 not expected to disrupt LIMS2 protein function with a negative predictive value of 80%. 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