5-179345258-GGCAGCAGCAGCA-GGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014244.5(ADAMTS2):c.53_70dupTGCTGCTGCTGCTGCTGC(p.Leu18_Leu23dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 146,980 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 28)
Exomes 𝑓: 0.0000040 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ADAMTS2
NM_014244.5 conservative_inframe_insertion
NM_014244.5 conservative_inframe_insertion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.00
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADAMTS2 | NM_014244.5 | c.53_70dupTGCTGCTGCTGCTGCTGC | p.Leu18_Leu23dup | conservative_inframe_insertion | 1/22 | ENST00000251582.12 | NP_055059.2 | |
ADAMTS2 | NM_021599.4 | c.53_70dupTGCTGCTGCTGCTGCTGC | p.Leu18_Leu23dup | conservative_inframe_insertion | 1/11 | NP_067610.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADAMTS2 | ENST00000251582.12 | c.53_70dupTGCTGCTGCTGCTGCTGC | p.Leu18_Leu23dup | conservative_inframe_insertion | 1/22 | 1 | NM_014244.5 | ENSP00000251582.7 | ||
ADAMTS2 | ENST00000274609.5 | c.53_70dupTGCTGCTGCTGCTGCTGC | p.Leu18_Leu23dup | conservative_inframe_insertion | 1/11 | 1 | ENSP00000274609.5 | |||
ADAMTS2 | ENST00000518335.3 | c.53_70dupTGCTGCTGCTGCTGCTGC | p.Leu18_Leu23dup | conservative_inframe_insertion | 1/21 | 3 | ENSP00000489888.2 | |||
ADAMTS2 | ENST00000698889.1 | n.53_70dupTGCTGCTGCTGCTGCTGC | non_coding_transcript_exon_variant | 1/21 | ENSP00000514008.1 |
Frequencies
GnomAD3 genomes AF: 0.0000204 AC: 3AN: 146980Hom.: 0 Cov.: 28
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000404 AC: 4AN: 989358Hom.: 0 Cov.: 29 AF XY: 0.00000212 AC XY: 1AN XY: 472146
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GnomAD4 genome AF: 0.0000204 AC: 3AN: 146980Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 71540
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ClinVar
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at