chr6-129507513-G-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_000426.4(LAMA2):āc.8728G>Cā(p.Val2910Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V2910I) has been classified as Likely benign.
Frequency
Consequence
NM_000426.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.8728G>C | p.Val2910Leu | missense_variant | 62/65 | ENST00000421865.3 | |
LOC102723409 | XR_001743860.2 | n.12103-4722C>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.8728G>C | p.Val2910Leu | missense_variant | 62/65 | 5 | NM_000426.4 | ||
ENST00000665046.1 | n.789-4722C>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251190Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135748
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461834Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727226
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74340
ClinVar
Submissions by phenotype
LAMA2-related muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 27, 2022 | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2910 of the LAMA2 protein (p.Val2910Leu). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with LAMA2-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt LAMA2 protein function. 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