rs901254
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_014244.5(ADAMTS2):c.688+601G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 152,294 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.027 ( 131 hom., cov: 33)
Consequence
ADAMTS2
NM_014244.5 intron
NM_014244.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.166
Genes affected
ADAMTS2 (HGNC:218): (ADAM metallopeptidase with thrombospondin type 1 motif 2) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature procollagen N-proteinase. This proteinase excises the N-propeptide of the fibrillar procollagens types I-III and type V. Mutations in this gene cause Ehlers-Danlos syndrome type VIIC, a recessively inherited connective-tissue disorder. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0273 (4151/152294) while in subpopulation NFE AF= 0.0339 (2304/68024). AF 95% confidence interval is 0.0327. There are 131 homozygotes in gnomad4. There are 2245 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 131 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAMTS2 | NM_014244.5 | c.688+601G>A | intron_variant | ENST00000251582.12 | |||
ADAMTS2 | NM_021599.4 | c.688+601G>A | intron_variant | ||||
ADAMTS2 | XM_047417895.1 | c.193+601G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTS2 | ENST00000251582.12 | c.688+601G>A | intron_variant | 1 | NM_014244.5 | P2 | |||
ADAMTS2 | ENST00000274609.5 | c.688+601G>A | intron_variant | 1 | |||||
ADAMTS2 | ENST00000518335.3 | c.688+601G>A | intron_variant | 3 | A2 | ||||
ADAMTS2 | ENST00000698889.1 | c.688+601G>A | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0273 AC: 4151AN: 152176Hom.: 131 Cov.: 33
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.0273 AC: 4151AN: 152294Hom.: 131 Cov.: 33 AF XY: 0.0302 AC XY: 2245AN XY: 74452
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3478
ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at