rs117222015
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_014244.5(ADAMTS2):c.764G>A(p.Arg255Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,613,770 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. R255R) has been classified as Likely benign.
Frequency
Consequence
NM_014244.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAMTS2 | NM_014244.5 | c.764G>A | p.Arg255Gln | missense_variant | 4/22 | ENST00000251582.12 | |
ADAMTS2 | NM_021599.4 | c.764G>A | p.Arg255Gln | missense_variant | 4/11 | ||
ADAMTS2 | XM_047417895.1 | c.269G>A | p.Arg90Gln | missense_variant | 3/21 | ||
ADAMTS2 | XM_047417896.1 | c.-119G>A | 5_prime_UTR_variant | 2/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTS2 | ENST00000251582.12 | c.764G>A | p.Arg255Gln | missense_variant | 4/22 | 1 | NM_014244.5 | P2 | |
ADAMTS2 | ENST00000274609.5 | c.764G>A | p.Arg255Gln | missense_variant | 4/11 | 1 | |||
ADAMTS2 | ENST00000518335.3 | c.764G>A | p.Arg255Gln | missense_variant | 4/21 | 3 | A2 | ||
ADAMTS2 | ENST00000698889.1 | c.764G>A | p.Arg255Gln | missense_variant, NMD_transcript_variant | 4/21 |
Frequencies
GnomAD3 genomes ? AF: 0.000854 AC: 130AN: 152224Hom.: 1 Cov.: 34
GnomAD3 exomes AF: 0.00202 AC: 508AN: 251320Hom.: 5 AF XY: 0.00218 AC XY: 296AN XY: 135906
GnomAD4 exome AF: 0.00111 AC: 1625AN: 1461428Hom.: 13 Cov.: 62 AF XY: 0.00128 AC XY: 927AN XY: 727028
GnomAD4 genome ? AF: 0.000853 AC: 130AN: 152342Hom.: 1 Cov.: 34 AF XY: 0.000940 AC XY: 70AN XY: 74496
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, dermatosparaxis type Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 21, 2019 | - - |
Likely benign, 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | ADAMTS2: BP4, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 02, 2020 | - - |
ADAMTS2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 17, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Ehlers-Danlos syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Nov 17, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at