5-179343878-G-C
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_014244.5(ADAMTS2):c.423C>G(p.Gly141Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G141G) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.000047 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ADAMTS2
NM_014244.5 synonymous
NM_014244.5 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.669
Publications
0 publications found
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]
ADAMTS2 Gene-Disease associations (from GenCC):
- Ehlers-Danlos syndrome, dermatosparaxis typeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, G2P, PanelApp Australia, Illumina
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP7
Synonymous conserved (PhyloP=-0.669 with no splicing effect.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| ADAMTS2 | ENST00000251582.12 | c.423C>G | p.Gly141Gly | synonymous_variant | Exon 2 of 22 | 1 | NM_014244.5 | ENSP00000251582.7 | ||
| ADAMTS2 | ENST00000274609.5 | c.423C>G | p.Gly141Gly | synonymous_variant | Exon 2 of 11 | 1 | ENSP00000274609.5 | |||
| ADAMTS2 | ENST00000518335.3 | c.423C>G | p.Gly141Gly | synonymous_variant | Exon 2 of 21 | 3 | ENSP00000489888.2 | |||
| ADAMTS2 | ENST00000698889.1 | n.423C>G | non_coding_transcript_exon_variant | Exon 2 of 21 | ENSP00000514008.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
34
GnomAD2 exomes AF: 0.000294 AC: 57AN: 194052 AF XY: 0.000273 show subpopulations
GnomAD2 exomes
AF:
AC:
57
AN:
194052
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000467 AC: 67AN: 1434750Hom.: 0 Cov.: 75 AF XY: 0.0000548 AC XY: 39AN XY: 711594 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
67
AN:
1434750
Hom.:
Cov.:
75
AF XY:
AC XY:
39
AN XY:
711594
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33038
American (AMR)
AF:
AC:
31
AN:
38836
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25564
East Asian (EAS)
AF:
AC:
6
AN:
38014
South Asian (SAS)
AF:
AC:
3
AN:
83080
European-Finnish (FIN)
AF:
AC:
8
AN:
49602
Middle Eastern (MID)
AF:
AC:
0
AN:
5610
European-Non Finnish (NFE)
AF:
AC:
17
AN:
1101606
Other (OTH)
AF:
AC:
2
AN:
59400
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.290
Heterozygous variant carriers
0
7
13
20
26
33
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
34
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
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
Publications
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