rs398123388
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PP3_StrongPP5
The NM_000426.4(LAMA2):c.830C>T(p.Ser277Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,607,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/20 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S277S) has been classified as Likely benign.
Frequency
Consequence
NM_000426.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.830C>T | p.Ser277Leu | missense_variant | 6/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.830C>T | p.Ser277Leu | missense_variant | 6/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.830C>T | p.Ser277Leu | missense_variant | 6/65 | 5 | NM_000426.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152038Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250744Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135498
GnomAD4 exome AF: 0.00000824 AC: 12AN: 1455548Hom.: 0 Cov.: 29 AF XY: 0.00000828 AC XY: 6AN XY: 724442
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152038Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74280
ClinVar
Submissions by phenotype
Merosin deficient congenital muscular dystrophy Pathogenic:1Uncertain:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jul 27, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Oct 16, 2017 | - - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 22, 2013 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 06, 2019 | - - |
Muscular dystrophy, limb-girdle, autosomal recessive 23 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Hadassah Hebrew University Medical Center | - | - - |
LAMA2-related muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 08, 2022 | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 277 of the LAMA2 protein (p.Ser277Leu). This variant is present in population databases (rs398123388, gnomAD 0.01%). This missense change has been observed in individual(s) with LAMA2-related muscular dystrophy (PMID: 24225367). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 92990). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at