rs79330641
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_014244.5(ADAMTS2):c.3014C>T(p.Ala1005Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,552,394 control chromosomes in the GnomAD database, including 23 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1005T) has been classified as Uncertain significance.
Frequency
Consequence
NM_014244.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.3014C>T | p.Ala1005Val | missense_variant | 20/22 | ENST00000251582.12 | |
ADAMTS2 | XM_047417895.1 | c.2519C>T | p.Ala840Val | missense_variant | 19/21 | ||
ADAMTS2 | XM_047417896.1 | c.2132C>T | p.Ala711Val | missense_variant | 18/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTS2 | ENST00000251582.12 | c.3014C>T | p.Ala1005Val | missense_variant | 20/22 | 1 | NM_014244.5 | P2 | |
ADAMTS2 | ENST00000518335.3 | c.3014C>T | p.Ala1005Val | missense_variant | 20/21 | 3 | A2 | ||
ADAMTS2 | ENST00000523450.1 | n.122C>T | non_coding_transcript_exon_variant | 1/3 | 2 | ||||
ADAMTS2 | ENST00000698889.1 | c.*224C>T | 3_prime_UTR_variant, NMD_transcript_variant | 20/21 |
Frequencies
GnomAD3 genomes AF: 0.00671 AC: 1022AN: 152224Hom.: 13 Cov.: 33
GnomAD3 exomes AF: 0.00161 AC: 253AN: 157232Hom.: 3 AF XY: 0.00126 AC XY: 105AN XY: 83122
GnomAD4 exome AF: 0.000805 AC: 1127AN: 1400052Hom.: 10 Cov.: 31 AF XY: 0.000705 AC XY: 487AN XY: 690698
GnomAD4 genome AF: 0.00671 AC: 1022AN: 152342Hom.: 13 Cov.: 33 AF XY: 0.00647 AC XY: 482AN XY: 74492
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, dermatosparaxis type Benign:3
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 02, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Ehlers-Danlos syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Dec 01, 2019 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 14, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at