rs118203899
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_005562.3(LAMC2):āc.1065C>Gā(p.Tyr355Ter) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,426,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely pathogenic (ā ā ). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_005562.3 stop_gained, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMC2 | NM_005562.3 | c.1065C>G | p.Tyr355Ter | stop_gained, splice_region_variant | 8/23 | ENST00000264144.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMC2 | ENST00000264144.5 | c.1065C>G | p.Tyr355Ter | stop_gained, splice_region_variant | 8/23 | 1 | NM_005562.3 | P1 | |
LAMC2 | ENST00000493293.5 | c.1065C>G | p.Tyr355Ter | stop_gained, splice_region_variant | 8/22 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 7.01e-7 AC: 1AN: 1426312Hom.: 0 Cov.: 25 AF XY: 0.00000140 AC XY: 1AN XY: 711810
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Junctional epidermolysis bullosa gravis of Herlitz Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Mar 18, 2016 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 10, 2019 | Variant summary: LAMC2 c.1065C>G (p.Tyr355X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251430 control chromosomes (gnomAD). c.1065C>G has been reported in the literature in multiple homozygous individuals affected with Junctional Epidermolysis Bullosa from Italy (Baudoin_1994, Castori_2008). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. - |
Epidermolysis bullosa, junctional 3B, severe Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 1994 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at