rs137853147
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_014244.5(ADAMTS2):c.2384G>A(p.Trp795Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. 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 Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
ADAMTS2
NM_014244.5 stop_gained
NM_014244.5 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 7.79
Genes affected
ADAMTS2 (HGNC:218): (ADAM metallopeptidase with thrombospondin type 1 motif 2) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature procollagen N-proteinase. This proteinase excises the N-propeptide of the fibrillar procollagens types I-III and type V. Mutations in this gene cause Ehlers-Danlos syndrome type VIIC, a recessively inherited connective-tissue disorder. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 5-179130005-C-T is Pathogenic according to our data. Variant chr5-179130005-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 5503.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAMTS2 | NM_014244.5 | c.2384G>A | p.Trp795Ter | stop_gained | 16/22 | ENST00000251582.12 | |
ADAMTS2 | XM_047417895.1 | c.1889G>A | p.Trp630Ter | stop_gained | 15/21 | ||
ADAMTS2 | XM_047417896.1 | c.1502G>A | p.Trp501Ter | stop_gained | 14/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTS2 | ENST00000251582.12 | c.2384G>A | p.Trp795Ter | stop_gained | 16/22 | 1 | NM_014244.5 | P2 | |
ADAMTS2 | ENST00000518335.3 | c.2384G>A | p.Trp795Ter | stop_gained | 16/21 | 3 | A2 | ||
ADAMTS2 | ENST00000698889.1 | c.2384G>A | p.Trp795Ter | stop_gained, NMD_transcript_variant | 16/21 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Ehlers-Danlos syndrome, dermatosparaxis type Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Oct 18, 2016 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 1999 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A
Vest4
GERP RS
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