rs1554228141
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PS1PM2
The NM_000426.4(LAMA2):c.1084_1085delinsTT(p.Arg362Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Pathogenicin Lovd.
Frequency
Genomes: not found (cov: 32)
Consequence
LAMA2
NM_000426.4 missense
NM_000426.4 missense
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.47
Genes affected
LAMA2 (HGNC:6482): (laminin subunit alpha 2) Laminin, an extracellular protein, is a major component of the basement membrane. It is thought to mediate the attachment, migration, and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. It is composed of three subunits, alpha, beta, and gamma, which are bound to each other by disulfide bonds into a cross-shaped molecule. This gene encodes the alpha 2 chain, which constitutes one of the subunits of laminin 2 (merosin) and laminin 4 (s-merosin). Mutations in this gene have been identified as the cause of congenital merosin-deficient muscular dystrophy. Two transcript variants encoding different proteins have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PS1
Transcript NM_000426.4 (LAMA2) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in Lovd
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.1084_1085delinsTT | p.Arg362Leu | missense_variant | 8/65 | ENST00000421865.3 | NP_000417.3 | |
LAMA2 | NM_001079823.2 | c.1084_1085delinsTT | p.Arg362Leu | missense_variant | 8/64 | NP_001073291.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.1084_1085delinsTT | p.Arg362Leu | missense_variant | 8/65 | 5 | NM_000426.4 | ENSP00000400365 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
LAMA2-related muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 17, 2022 | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 362 of the LAMA2 protein (p.Arg362Leu). This variant is present in population databases (no rsID available, gnomAD 2.2%). This variant has not been reported in the literature in individuals affected with LAMA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 543853). 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: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). 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:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at