rs201307156
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_005562.3(LAMC2):c.3385C>T(p.Arg1129Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,782 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 Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R1129R) has been classified as Likely benign.
Frequency
Consequence
NM_005562.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMC2 | NM_005562.3 | c.3385C>T | p.Arg1129Ter | stop_gained | 23/23 | ENST00000264144.5 | |
LAMC2 | XM_047420358.1 | c.3328+2812C>T | intron_variant | ||||
LAMC2 | XM_047420361.1 | c.3328+2812C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMC2 | ENST00000264144.5 | c.3385C>T | p.Arg1129Ter | stop_gained | 23/23 | 1 | NM_005562.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251140Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135744
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461782Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727190
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Junctional epidermolysis bullosa, non-Herlitz type Pathogenic:1
Pathogenic, no assertion criteria provided | research | Department of Pediatrics, Division of Medical Genetics, Faculty of Medicine Ramathibodi Hospital, Mahidol University | Dec 08, 2020 | - - |
Junctional epidermolysis bullosa gravis of Herlitz Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | May 24, 2016 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | This sequence change creates a premature translational stop signal (p.Arg1129*) in the LAMC2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 65 amino acid(s) of the LAMC2 protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with LAMC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 370953). This variant disrupts a region of the LAMC2 protein in which other variant(s) (p.Thr1132Asnfs*38) have been determined to be pathogenic (PMID: 11564184). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at