rs376437110
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_000426.4(LAMA2):c.745C>T(p.Arg249Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,612,472 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. R249H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000426.4 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 |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.745C>T | p.Arg249Cys | missense_variant | 5/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.745C>T | p.Arg249Cys | missense_variant | 5/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.745C>T | p.Arg249Cys | missense_variant | 5/65 | 5 | NM_000426.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 151880Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250766Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135518
GnomAD4 exome AF: 0.00000959 AC: 14AN: 1460592Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 726616
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 151880Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74190
ClinVar
Submissions by phenotype
LAMA2-related muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 29, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 249 of the LAMA2 protein (p.Arg249Cys). This variant is present in population databases (rs376437110, gnomAD 0.003%). This missense change has been observed in individual(s) with congenital muscular dystrophy (PMID: 30055037). ClinVar contains an entry for this variant (Variation ID: 477505). 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: "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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 13, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at