rs148737005
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014244.5(ADAMTS2):c.859G>A(p.Val287Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000513 in 1,462,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAMTS2 | NM_014244.5 | c.859G>A | p.Val287Ile | missense_variant | 4/22 | ENST00000251582.12 | |
ADAMTS2 | NM_021599.4 | c.859G>A | p.Val287Ile | missense_variant | 4/11 | ||
ADAMTS2 | XM_047417895.1 | c.364G>A | p.Val122Ile | missense_variant | 3/21 | ||
ADAMTS2 | XM_047417896.1 | c.-24G>A | 5_prime_UTR_variant | 2/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTS2 | ENST00000251582.12 | c.859G>A | p.Val287Ile | missense_variant | 4/22 | 1 | NM_014244.5 | P2 | |
ADAMTS2 | ENST00000274609.5 | c.859G>A | p.Val287Ile | missense_variant | 4/11 | 1 | |||
ADAMTS2 | ENST00000518335.3 | c.859G>A | p.Val287Ile | missense_variant | 4/21 | 3 | A2 | ||
ADAMTS2 | ENST00000698889.1 | c.859G>A | p.Val287Ile | missense_variant, NMD_transcript_variant | 4/21 |
Frequencies
GnomAD3 genomes ? AF: 0.0000479 AC: 7AN: 146118Hom.: 0 Cov.: 29
GnomAD3 exomes AF: 0.0000757 AC: 19AN: 251078Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135830
GnomAD4 exome AF: 0.0000517 AC: 68AN: 1315890Hom.: 0 Cov.: 44 AF XY: 0.0000475 AC XY: 31AN XY: 652998
GnomAD4 genome ? AF: 0.0000479 AC: 7AN: 146118Hom.: 0 Cov.: 29 AF XY: 0.0000281 AC XY: 2AN XY: 71096
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, dermatosparaxis type Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 15, 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. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 28, 2021 | This sequence change replaces valine with isoleucine at codon 287 of the ADAMTS2 protein (p.Val287Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs148737005, ExAC 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: 537399). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 11, 2023 | The c.859G>A (p.V287I) alteration is located in exon 4 (coding exon 4) of the ADAMTS2 gene. This alteration results from a G to A substitution at nucleotide position 859, causing the valine (V) at amino acid position 287 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at