rs781728421
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_000426.4(LAMA2):c.1787C>T(p.Pro596Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,589,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.1787C>T | p.Pro596Leu | missense_variant | 13/65 | ENST00000421865.3 | NP_000417.3 | |
LAMA2 | NM_001079823.2 | c.1787C>T | p.Pro596Leu | missense_variant | 13/64 | NP_001073291.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.1787C>T | p.Pro596Leu | missense_variant | 13/65 | 5 | NM_000426.4 | ENSP00000400365.2 | ||
LAMA2 | ENST00000618192.5 | c.1787C>T | p.Pro596Leu | missense_variant | 13/66 | 5 | ENSP00000480802.2 | |||
LAMA2 | ENST00000617695.5 | c.1787C>T | p.Pro596Leu | missense_variant | 13/64 | 5 | ENSP00000481744.2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152162Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251102Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135698
GnomAD4 exome AF: 0.0000167 AC: 24AN: 1437206Hom.: 0 Cov.: 27 AF XY: 0.0000195 AC XY: 14AN XY: 716804
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152280Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74452
ClinVar
Submissions by phenotype
LAMA2-related muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 24, 2021 | This sequence change replaces proline with leucine at codon 596 of the LAMA2 protein (p.Pro596Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs781728421, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with LAMA2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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