rs768056213
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_001161403.3(LIMS2):c.290C>T(p.Pro97Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000942 in 1,614,012 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P97S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001161403.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.290C>T | p.Pro97Leu | missense_variant | 4/10 | ENST00000355119.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LIMS2 | ENST00000355119.9 | c.290C>T | p.Pro97Leu | missense_variant | 4/10 | 1 | NM_001161403.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251406Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135878
GnomAD4 exome AF: 0.0000999 AC: 146AN: 1461798Hom.: 0 Cov.: 33 AF XY: 0.0000949 AC XY: 69AN XY: 727204
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74350
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 | Apr 12, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 11, 2017 | This variant has been reported in a family affected with autosomal recessive limb-girdle muscular dystrophy, it was found to be in cis with c.342C>G (p.N114K) and in trans with c.1034T>C (p.L345P) (PMID: 25589244). This variant is also known as c.356C>T, p.P119L in NM_001136037.2 in the literature. ClinVar contains an entry for this variant (Variation ID: 222901). This variant is present in population databases (rs768056213, ExAC 0.006%). This sequence change replaces proline with leucine at codon 121 of the LIMS2 protein (p.Pro121Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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