chr3-48573047-C-T
Variant summary
Our verdict is Pathogenic. Variant got 17 ACMG points: 17P and 0B. PS1PM1PM2PM5PP2PP3_StrongPP5_Moderate
The NM_000094.4(COL7A1):c.6724G>A(p.Gly2242Arg) variant causes a missense change. 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 (★). Another nucleotide change resulting in same amino acid change has been previously reported as Pathogenicin ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G2242E) has been classified as Pathogenic.
Frequency
Consequence
NM_000094.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL7A1 | NM_000094.4 | c.6724G>A | p.Gly2242Arg | missense_variant | 86/119 | ENST00000681320.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL7A1 | ENST00000681320.1 | c.6724G>A | p.Gly2242Arg | missense_variant | 86/119 | NM_000094.4 | P1 | ||
COL7A1 | ENST00000328333.12 | c.6724G>A | p.Gly2242Arg | missense_variant | 85/118 | 1 | P1 | ||
COL7A1 | ENST00000487017.5 | n.2641G>A | non_coding_transcript_exon_variant | 51/83 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 37
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Epidermolysis bullosa pruriginosa, autosomal dominant Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 1999 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Sep 19, 2023 | Located in the highly conserved Gly-X-Y repeat of the collagenous domain; Glycine substitution variants in this region of the COLVII protein destabilize the collagen triple helix resulting in skin fragility due to poor anchoring of the basement membrane to the underlying dermis (Pfendner and Lucky, 2018); Same amino acid substitution caused by a different nucleotide change (c.724G>C) has been reported as pathogenic in the published literature and at GeneDx in association with DEB (Iglesias et al., 2014; Farwell et al., 2015); A different missense change at this residue (p.(G2242E)) has been reported as pathogenic in the published literature and at GeneDx in association with DEB (Whittock et al., 1999; Murase et al., 2011; Almaani et al., 2011); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25525159, 25356970, 24901346, 18558993, 10383749, 9182828, 21448560, 10504458, 21629976) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at