rs200022037
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The ENST00000251582.12(ADAMTS2):c.3343G>A(p.Asp1115Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000144 in 1,612,558 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign 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. D1115H) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000251582.12 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADAMTS2 | NM_014244.5 | c.3343G>A | p.Asp1115Asn | missense_variant | 22/22 | ENST00000251582.12 | NP_055059.2 | |
ADAMTS2 | XM_047417895.1 | c.2848G>A | p.Asp950Asn | missense_variant | 21/21 | XP_047273851.1 | ||
ADAMTS2 | XM_047417896.1 | c.2461G>A | p.Asp821Asn | missense_variant | 20/20 | XP_047273852.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADAMTS2 | ENST00000251582.12 | c.3343G>A | p.Asp1115Asn | missense_variant | 22/22 | 1 | NM_014244.5 | ENSP00000251582 | P2 | |
ADAMTS2 | ENST00000522937.1 | n.359G>A | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000210 AC: 32AN: 152148Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.000124 AC: 31AN: 250914Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135586
GnomAD4 exome AF: 0.000138 AC: 201AN: 1460290Hom.: 0 Cov.: 32 AF XY: 0.000145 AC XY: 105AN XY: 726110
GnomAD4 genome AF: 0.000210 AC: 32AN: 152268Hom.: 2 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74444
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, dermatosparaxis type Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 17, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 01, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1115 of the ADAMTS2 protein (p.Asp1115Asn). This variant is present in population databases (rs200022037, gnomAD 0.02%). 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: 546992). 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 tolerated. 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 | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 12, 2021 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at