6-129267114-G-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000426.4(LAMA2):c.2217G>A(p.Trp739*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000426.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.2217G>A | p.Trp739* | stop_gained | Exon 16 of 65 | 5 | NM_000426.4 | ENSP00000400365.2 | ||
LAMA2 | ENST00000618192.5 | c.2217G>A | p.Trp739* | stop_gained | Exon 16 of 66 | 5 | ENSP00000480802.2 | |||
LAMA2 | ENST00000617695.5 | c.2217G>A | p.Trp739* | stop_gained | Exon 16 of 64 | 5 | ENSP00000481744.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Merosin deficient congenital muscular dystrophy Pathogenic:1
The variant was identified at homozygous state by Targeted next-generation sequencing of muscular dystrophies gene panel. It was confirmed by Sanger sequencing. Both parents present the variant at heterozygous state. This variant has never been reported in public human databases (accessed, Nov 2020) It was also not found in an in-house database of 100 Moroccan exomes (personal data). This variant is in agreement with the clinical data of a patient who presents a severe phenotype of MDC1A. -
not provided Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at