chr6-129453121-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_000426.4(LAMA2):c.6563G>A(p.Ser2188Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00016 in 1,612,686 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S2188T) has been classified as Uncertain significance.
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.6563G>A | p.Ser2188Asn | missense_variant | 46/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.6563G>A | p.Ser2188Asn | missense_variant | 46/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.6563G>A | p.Ser2188Asn | missense_variant | 46/65 | 5 | NM_000426.4 | ||
ENST00000665046.1 | n.976-11869C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000124 AC: 31AN: 250708Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135540
GnomAD4 exome AF: 0.000168 AC: 245AN: 1460422Hom.: 0 Cov.: 30 AF XY: 0.000172 AC XY: 125AN XY: 726586
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152264Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74444
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 10, 2022 | 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) | Dec 20, 2012 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Apr 06, 2021 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 16, 2024 | Variant summary: LAMA2 c.6563G>A (p.Ser2188Asn) results in a conservative amino acid change located in the Laminin G domain (IPR001791) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00012 in 250708 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in LAMA2 causing Laminin Alpha 2-Related Dystrophy (0.00012 vs 0.0022), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.6563G>A in individuals affected with Laminin Alpha 2-Related Dystrophy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 92978). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Merosin deficient congenital muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jan 03, 2017 | - - |
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. - |
Merosin deficient congenital muscular dystrophy;C4748327:Muscular dystrophy, limb-girdle, autosomal recessive 23 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 03, 2022 | - - |
LAMA2-related muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at