rs200982805
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong
The NM_014244.5(ADAMTS2):āc.3449A>Gā(p.Asn1150Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,614,098 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_014244.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAMTS2 | NM_014244.5 | c.3449A>G | p.Asn1150Ser | missense_variant | 22/22 | ENST00000251582.12 | |
ADAMTS2 | XM_047417895.1 | c.2954A>G | p.Asn985Ser | missense_variant | 21/21 | ||
ADAMTS2 | XM_047417896.1 | c.2567A>G | p.Asn856Ser | missense_variant | 20/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTS2 | ENST00000251582.12 | c.3449A>G | p.Asn1150Ser | missense_variant | 22/22 | 1 | NM_014244.5 | P2 | |
ADAMTS2 | ENST00000522937.1 | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152086Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000135 AC: 34AN: 251496Hom.: 0 AF XY: 0.000147 AC XY: 20AN XY: 135922
GnomAD4 exome AF: 0.000168 AC: 246AN: 1461894Hom.: 1 Cov.: 32 AF XY: 0.000182 AC XY: 132AN XY: 727248
GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15AN XY: 74414
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, dermatosparaxis type Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 21, 2022 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1150 of the ADAMTS2 protein (p.Asn1150Ser). This variant is present in population databases (rs200982805, gnomAD 0.04%). 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: 353086). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | May 01, 2020 | - - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Nov 19, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 04, 2022 | 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