rs751283120
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_014244.5(ADAMTS2):c.1030C>T(p.Arg344Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,614,052 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R344H) has been classified as Uncertain significance.
Frequency
Consequence
NM_014244.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAMTS2 | NM_014244.5 | c.1030C>T | p.Arg344Cys | missense_variant | 6/22 | ENST00000251582.12 | |
ADAMTS2 | NM_021599.4 | c.1030C>T | p.Arg344Cys | missense_variant | 6/11 | ||
ADAMTS2 | XM_047417895.1 | c.535C>T | p.Arg179Cys | missense_variant | 5/21 | ||
ADAMTS2 | XM_047417896.1 | c.148C>T | p.Arg50Cys | missense_variant | 4/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTS2 | ENST00000251582.12 | c.1030C>T | p.Arg344Cys | missense_variant | 6/22 | 1 | NM_014244.5 | P2 | |
ADAMTS2 | ENST00000274609.5 | c.1030C>T | p.Arg344Cys | missense_variant | 6/11 | 1 | |||
ADAMTS2 | ENST00000518335.3 | c.1030C>T | p.Arg344Cys | missense_variant | 6/21 | 3 | A2 | ||
ADAMTS2 | ENST00000698889.1 | c.1030C>T | p.Arg344Cys | missense_variant, NMD_transcript_variant | 6/21 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251358Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135892
GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461834Hom.: 0 Cov.: 32 AF XY: 0.0000206 AC XY: 15AN XY: 727216
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74360
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, dermatosparaxis type Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 26, 2021 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 344 of the ADAMTS2 protein (p.Arg344Cys). This variant is present in population databases (rs751283120, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ADAMTS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 580145). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 27, 2023 | 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; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | May 26, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at