chr6-129465266-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_000426.4(LAMA2):c.7277C>T(p.Thr2426Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,611,174 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 (★).
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
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151880Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249986Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135084
GnomAD4 exome AF: 0.0000349 AC: 51AN: 1459294Hom.: 0 Cov.: 30 AF XY: 0.0000344 AC XY: 25AN XY: 726008
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151880Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74164
ClinVar
Submissions by phenotype
LAMA2-related muscular dystrophy Uncertain:1
This sequence change replaces threonine with isoleucine at codon 2426 of the LAMA2 protein (p.Thr2426Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with LAMA2-related disease. 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