rs118203900
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_005562.3(LAMC2):c.1659C>A(p.Cys553Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,880 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 (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_005562.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMC2 | NM_005562.3 | c.1659C>A | p.Cys553Ter | stop_gained | 11/23 | ENST00000264144.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMC2 | ENST00000264144.5 | c.1659C>A | p.Cys553Ter | stop_gained | 11/23 | 1 | NM_005562.3 | P1 | |
LAMC2 | ENST00000493293.5 | c.1659C>A | p.Cys553Ter | stop_gained | 11/22 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461880Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727238
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 05, 2018 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in LAMC2 are known to be pathogenic (PMID: 11907499, 16473856). This variant has been observed to be homozygous in an individual affected with junctional epidermolysis bullosa (PMID: 10951251). ClinVar contains an entry for this variant (Variation ID: 14557). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Cys553*) in the LAMC2 gene. It is expected to result in an absent or disrupted protein product. - |
Epidermolysis bullosa, junctional 3B, severe Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2000 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at