rs140022033
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_014244.5(ADAMTS2):c.2795G>A(p.Arg932Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,612,998 control chromosomes in the GnomAD database, including 1 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R932W) has been classified as Uncertain significance.
Frequency
Consequence
NM_014244.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAMTS2 | NM_014244.5 | c.2795G>A | p.Arg932Gln | missense_variant | 19/22 | ENST00000251582.12 | |
ADAMTS2 | XM_047417895.1 | c.2300G>A | p.Arg767Gln | missense_variant | 18/21 | ||
ADAMTS2 | XM_047417896.1 | c.1913G>A | p.Arg638Gln | missense_variant | 17/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTS2 | ENST00000251582.12 | c.2795G>A | p.Arg932Gln | missense_variant | 19/22 | 1 | NM_014244.5 | P2 | |
ADAMTS2 | ENST00000518335.3 | c.2795G>A | p.Arg932Gln | missense_variant | 19/21 | 3 | A2 | ||
ADAMTS2 | ENST00000698889.1 | c.2795G>A | p.Arg932Gln | missense_variant, NMD_transcript_variant | 19/21 |
Frequencies
GnomAD3 genomes ? AF: 0.00101 AC: 154AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00113 AC: 284AN: 250274Hom.: 0 AF XY: 0.00107 AC XY: 145AN XY: 135466
GnomAD4 exome AF: 0.00123 AC: 1795AN: 1460660Hom.: 1 Cov.: 37 AF XY: 0.00125 AC XY: 911AN XY: 726680
GnomAD4 genome ? AF: 0.00101 AC: 154AN: 152338Hom.: 0 Cov.: 33 AF XY: 0.000967 AC XY: 72AN XY: 74486
ClinVar
Submissions by phenotype
not provided Benign:4
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 28, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | ADAMTS2: BP4 - |
Ehlers-Danlos syndrome, dermatosparaxis type Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 | - - |
Ehlers-Danlos syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Nov 23, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at