rs56173620
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000426.4(LAMA2):c.5530C>A(p.Arg1844Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 1,610,812 control chromosomes in the GnomAD database, including 250 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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. R1844C) has been classified as Likely benign.
Frequency
Consequence
NM_000426.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.5530C>A | p.Arg1844Ser | missense_variant | 38/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.5530C>A | p.Arg1844Ser | missense_variant | 38/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.5530C>A | p.Arg1844Ser | missense_variant | 38/65 | 5 | NM_000426.4 | ||
LAMA2 | ENST00000618192.5 | c.5794C>A | p.Arg1932Ser | missense_variant | 39/66 | 5 | P1 | ||
LAMA2 | ENST00000617695.5 | c.5530C>A | p.Arg1844Ser | missense_variant | 38/64 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0100 AC: 1525AN: 152130Hom.: 9 Cov.: 33
GnomAD3 exomes AF: 0.0104 AC: 2604AN: 250736Hom.: 29 AF XY: 0.0106 AC XY: 1442AN XY: 135504
GnomAD4 exome AF: 0.0160 AC: 23366AN: 1458564Hom.: 241 Cov.: 31 AF XY: 0.0157 AC XY: 11428AN XY: 725826
GnomAD4 genome ? AF: 0.0100 AC: 1524AN: 152248Hom.: 9 Cov.: 33 AF XY: 0.00916 AC XY: 682AN XY: 74448
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 04, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 17, 2022 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | LAMA2: BP4, BS1, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Feb 11, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 18, 2019 | This variant is associated with the following publications: (PMID: 20207543, 9541105, 25256590, 27535533, 29706646) - |
Polymicrogyria Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | Sep 01, 2017 | this variant was indentified in an individual with malformations of cortical development - |
Merosin deficient congenital muscular dystrophy Benign:1
Benign, criteria provided, single submitter | research | Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard | - | The heterozygous p.Arg1844Ser variant in LAMA2 has been reported in the compound heterozygous state, with a splice site mutation, in an individual with congenital muscular dystrophy (PMID: 20207543), but has also been identified in >1% of European (non-Finnish) chromosomes and 18 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for autosomal recessive congenital muscular dystrophy. - |
LAMA2-related muscular dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Congenital muscular dystrophy due to partial LAMA2 deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 08, 2018 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at