rs121912850
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Moderate
The NM_000094.4(COL7A1):c.6227G>A(p.Gly2076Asp) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. G2076S) has been classified as Likely pathogenic.
Frequency
Genomes: not found (cov: 33)
Consequence
COL7A1
NM_000094.4 missense
NM_000094.4 missense
Scores
11
6
2
Clinical Significance
Conservation
PhyloP100: 4.06
Genes affected
COL7A1 (HGNC:2214): (collagen type VII alpha 1 chain) This gene encodes the alpha chain of type VII collagen. The type VII collagen fibril, composed of three identical alpha collagen chains, is restricted to the basement zone beneath stratified squamous epithelia. It functions as an anchoring fibril between the external epithelia and the underlying stroma. Mutations in this gene are associated with all forms of dystrophic epidermolysis bullosa. In the absence of mutations, however, an acquired form of this disease can result from an autoimmune response made to type VII collagen. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 13 ACMG points.
PM1
?
In a hotspot region, there are 5 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 4 uncertain in NM_000094.4
PM2
?
Very rare variant in population databases, with high coverage;
PM5
?
Other missense variant is known to change same aminoacid residue: Variant chr3-48575117-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2861748.Status of the report is criteria_provided_single_submitter, 1 stars.
PP2
?
Missense variant where missense usually causes diseases, COL7A1
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.993
PP5
?
Variant 3-48575116-C-T is Pathogenic according to our data. Variant chr3-48575116-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 17457.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-48575116-C-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL7A1 | NM_000094.4 | c.6227G>A | p.Gly2076Asp | missense_variant | 76/119 | ENST00000681320.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL7A1 | ENST00000681320.1 | c.6227G>A | p.Gly2076Asp | missense_variant | 76/119 | NM_000094.4 | P1 | ||
COL7A1 | ENST00000328333.12 | c.6227G>A | p.Gly2076Asp | missense_variant | 75/118 | 1 | P1 | ||
COL7A1 | ENST00000487017.5 | n.2144G>A | non_coding_transcript_exon_variant | 41/83 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 35
GnomAD4 exome
Cov.:
35
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Generalized dominant dystrophic epidermolysis bullosa Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Center for Research in Genodermatoses and Epidermolysis Bullosa, University of Buenos Aires | Mar 14, 2022 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 1997 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Benign
DEOGEN2
Pathogenic
D
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
A;A
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of glycosylation at P2081 (P = 0.0357);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at