chr6-129353285-C-T
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_000426.4(LAMA2):c.4645C>T(p.Arg1549Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000558 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R1549R) has been classified as Likely benign. 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 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.4645C>T | p.Arg1549Ter | stop_gained | 32/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.4645C>T | p.Arg1549Ter | stop_gained | 32/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.4645C>T | p.Arg1549Ter | stop_gained | 32/65 | 5 | NM_000426.4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152100Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251358Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135850
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461826Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727212
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74424
ClinVar
Submissions by phenotype
Merosin deficient congenital muscular dystrophy Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Apr 11, 2023 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | May 23, 2018 | - - |
LAMA2-related muscular dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 19, 2023 | This sequence change creates a premature translational stop signal (p.Arg1549*) in the LAMA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LAMA2 are known to be pathogenic (PMID: 18700894, 32904964). This variant is present in population databases (rs121913575, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with LAMA2-related conditions (PMID: 10852549, 20207543). ClinVar contains an entry for this variant (Variation ID: 14299). For these reasons, this variant has been classified as Pathogenic. - |
Congenital muscular dystrophy due to partial LAMA2 deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 24, 2000 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at