rs138964034
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PP3_Moderate
The NM_000426.4(LAMA2):c.410C>T(p.Ala137Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,613,776 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 (★★). Synonymous variant affecting the same amino acid position (i.e. A137A) has been classified as Benign.
Frequency
Consequence
NM_000426.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.410C>T | p.Ala137Val | missense_variant | 4/65 | ENST00000421865.3 | NP_000417.3 | |
LAMA2 | NM_001079823.2 | c.410C>T | p.Ala137Val | missense_variant | 4/64 | NP_001073291.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.410C>T | p.Ala137Val | missense_variant | 4/65 | 5 | NM_000426.4 | ENSP00000400365.2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151984Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251406Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135892
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461792Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727210
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151984Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74232
ClinVar
Submissions by phenotype
LAMA2-related muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 25, 2021 | This sequence change replaces alanine with valine at codon 137 of the LAMA2 protein (p.Ala137Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs138964034, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with LAMA2-related conditions. 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: "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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 13, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at