rs188566209
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_014244.5(ADAMTS2):c.2292C>T(p.Ala764Ala) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000214 in 1,613,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_014244.5 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADAMTS2 | NM_014244.5 | c.2292C>T | p.Ala764Ala | splice_region_variant, synonymous_variant | 16/22 | ENST00000251582.12 | NP_055059.2 | |
ADAMTS2 | XM_047417895.1 | c.1797C>T | p.Ala599Ala | splice_region_variant, synonymous_variant | 15/21 | XP_047273851.1 | ||
ADAMTS2 | XM_047417896.1 | c.1410C>T | p.Ala470Ala | splice_region_variant, synonymous_variant | 14/20 | XP_047273852.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADAMTS2 | ENST00000251582.12 | c.2292C>T | p.Ala764Ala | splice_region_variant, synonymous_variant | 16/22 | 1 | NM_014244.5 | ENSP00000251582.7 | ||
ADAMTS2 | ENST00000518335.3 | c.2292C>T | p.Ala764Ala | splice_region_variant, synonymous_variant | 16/21 | 3 | ENSP00000489888.2 | |||
ADAMTS2 | ENST00000698889.1 | n.2292C>T | splice_region_variant, non_coding_transcript_exon_variant | 16/21 | ENSP00000514008.1 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152218Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000717 AC: 18AN: 250998Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135816
GnomAD4 exome AF: 0.000225 AC: 329AN: 1461554Hom.: 0 Cov.: 32 AF XY: 0.000212 AC XY: 154AN XY: 727070
GnomAD4 genome AF: 0.000105 AC: 16AN: 152336Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74478
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, dermatosparaxis type Uncertain:1Benign:2
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 24, 2024 | - - |
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. - |
Ehlers-Danlos syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Dec 21, 2020 | - - |
ADAMTS2-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 28, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 17, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at