rs141920360
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_000426.4(LAMA2):āc.2831A>Gā(p.Gln944Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000539 in 1,613,644 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. Q944Q) has been classified as Likely benign.
Frequency
Consequence
NM_000426.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.2831A>G | p.Gln944Arg | missense_variant | 20/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.2831A>G | p.Gln944Arg | missense_variant | 20/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.2831A>G | p.Gln944Arg | missense_variant | 20/65 | 5 | NM_000426.4 | ||
LAMA2 | ENST00000618192.5 | c.2831A>G | p.Gln944Arg | missense_variant | 20/66 | 5 | P1 | ||
LAMA2 | ENST00000617695.5 | c.2831A>G | p.Gln944Arg | missense_variant | 20/64 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152238Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251446Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135910
GnomAD4 exome AF: 0.0000554 AC: 81AN: 1461406Hom.: 0 Cov.: 31 AF XY: 0.0000481 AC XY: 35AN XY: 727066
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152238Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74374
ClinVar
Submissions by phenotype
not provided Uncertain:4
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 12, 2023 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 31, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 22, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | May 13, 2022 | BP4, PM2 - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 22, 2022 | The c.2831A>G (p.Q944R) alteration is located in exon 20 (coding exon 20) of the LAMA2 gene. This alteration results from a A to G substitution at nucleotide position 2831, causing the glutamine (Q) at amino acid position 944 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
LAMA2-related muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 944 of the LAMA2 protein (p.Gln944Arg). This variant is present in population databases (rs141920360, gnomAD 0.008%). 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: 195461). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt LAMA2 protein function. 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. - |
Congenital muscular dystrophy due to partial LAMA2 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at