rs142536231
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6
The NM_000426.4(LAMA2):c.6692G>A(p.Arg2231His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000733 in 1,610,744 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2231G) has been classified as Uncertain significance.
Frequency
Consequence
NM_000426.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.6692G>A | p.Arg2231His | missense_variant | 47/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.6692G>A | p.Arg2231His | missense_variant | 47/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.6692G>A | p.Arg2231His | missense_variant | 47/65 | 5 | NM_000426.4 | ||
ENST00000665046.1 | n.976-13021C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152074Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000124 AC: 31AN: 250672Hom.: 0 AF XY: 0.000170 AC XY: 23AN XY: 135488
GnomAD4 exome AF: 0.0000734 AC: 107AN: 1458670Hom.: 1 Cov.: 29 AF XY: 0.0000799 AC XY: 58AN XY: 725780
GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152074Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6AN XY: 74274
ClinVar
Submissions by phenotype
Congenital muscular dystrophy due to partial LAMA2 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
LAMA2-related muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 10, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at