chr2-127643047-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001161403.3(LIMS2):āc.385C>Gā(p.Arg129Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000126 in 1,585,072 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R129C) has been classified as Likely benign.
Frequency
Consequence
NM_001161403.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LIMS2 | NM_001161403.3 | c.385C>G | p.Arg129Gly | missense_variant | 5/10 | ENST00000355119.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LIMS2 | ENST00000355119.9 | c.385C>G | p.Arg129Gly | missense_variant | 5/10 | 1 | NM_001161403.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152258Hom.: 0 Cov.: 34
GnomAD4 exome AF: 6.98e-7 AC: 1AN: 1432814Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 710018
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152258Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74380
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2W Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 30, 2021 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C45"). This variant has not been reported in the literature in individuals with LIMS2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glycine at codon 151 of the LIMS2 protein (p.Arg151Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at