rs149165006
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_000426.4(LAMA2):c.3154A>G(p.Ser1052Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000105 in 1,613,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 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. S1052N) 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.3154A>G | p.Ser1052Gly | missense_variant | 22/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.3154A>G | p.Ser1052Gly | missense_variant | 22/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.3154A>G | p.Ser1052Gly | missense_variant | 22/65 | 5 | NM_000426.4 | ||
LAMA2 | ENST00000618192.5 | c.3418A>G | p.Ser1140Gly | missense_variant | 23/66 | 5 | P1 | ||
LAMA2 | ENST00000617695.5 | c.3154A>G | p.Ser1052Gly | missense_variant | 22/64 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000578 AC: 88AN: 152174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000119 AC: 30AN: 251456Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135906
GnomAD4 exome AF: 0.0000554 AC: 81AN: 1461560Hom.: 0 Cov.: 32 AF XY: 0.0000591 AC XY: 43AN XY: 727106
GnomAD4 genome ? AF: 0.000578 AC: 88AN: 152292Hom.: 0 Cov.: 32 AF XY: 0.000604 AC XY: 45AN XY: 74476
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 27, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 11, 2017 | The S1052G variant has been previously reported in an individual with congenital muscular dystrophy who harbored an additional LAMA2 variant; however, segregation analysis to determine phase was not reported (Valencia et al., 2013). The S1052G variant is observed in 22/10,404 (0.21%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals; however, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with LAMA2-related disorders (Stenson et al., 2014). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. - |
LAMA2-related muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
LAMA2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 13, 2024 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at