rs2306942
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000426.4(LAMA2):c.3412G>A(p.Val1138Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0581 in 1,612,986 control chromosomes in the GnomAD database, including 3,884 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000426.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.3412G>A | p.Val1138Met | missense_variant, splice_region_variant | 24/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.3412G>A | p.Val1138Met | missense_variant, splice_region_variant | 24/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.3412G>A | p.Val1138Met | missense_variant, splice_region_variant | 24/65 | 5 | NM_000426.4 | ||
LAMA2 | ENST00000618192.5 | c.3676G>A | p.Val1226Met | missense_variant, splice_region_variant | 25/66 | 5 | P1 | ||
LAMA2 | ENST00000617695.5 | c.3412G>A | p.Val1138Met | missense_variant, splice_region_variant | 24/64 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0905 AC: 13757AN: 151978Hom.: 929 Cov.: 32
GnomAD3 exomes AF: 0.0651 AC: 16343AN: 251076Hom.: 816 AF XY: 0.0638 AC XY: 8664AN XY: 135716
GnomAD4 exome AF: 0.0547 AC: 79906AN: 1460890Hom.: 2951 Cov.: 32 AF XY: 0.0552 AC XY: 40139AN XY: 726772
GnomAD4 genome ? AF: 0.0907 AC: 13794AN: 152096Hom.: 933 Cov.: 32 AF XY: 0.0898 AC XY: 6680AN XY: 74376
ClinVar
Submissions by phenotype
not specified Benign:7
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 10, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 10, 2021 | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 19, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 20, 2016 | - - |
Merosin deficient congenital muscular dystrophy Benign:1
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
LAMA2-related muscular dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Congenital muscular dystrophy due to partial LAMA2 deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at