chr21-26838217-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_006988.5(ADAMTS1):c.2266C>T(p.Arg756Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000576 in 1,613,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R756Q) has been classified as Likely benign.
Frequency
Consequence
NM_006988.5 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 |
---|---|---|---|---|---|---|---|
ADAMTS1 | NM_006988.5 | c.2266C>T | p.Arg756Trp | missense_variant | 9/9 | ENST00000284984.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTS1 | ENST00000284984.8 | c.2266C>T | p.Arg756Trp | missense_variant | 9/9 | 1 | NM_006988.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000986 AC: 15AN: 152102Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000518 AC: 13AN: 250774Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135728
GnomAD4 exome AF: 0.0000534 AC: 78AN: 1461572Hom.: 0 Cov.: 31 AF XY: 0.0000495 AC XY: 36AN XY: 727064
GnomAD4 genome AF: 0.0000985 AC: 15AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74418
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 10, 2022 | The c.2266C>T (p.R756W) alteration is located in exon 9 (coding exon 9) of the ADAMTS1 gene. This alteration results from a C to T substitution at nucleotide position 2266, causing the arginine (R) at amino acid position 756 to be replaced by a tryptophan (W). 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