GeneBe

rs568040559

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014244.5(ADAMTS2):​c.56_70delTGCTGCTGCTGCTGC​(p.Leu19_Leu23del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000101 in 989,358 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: not found (cov: 28)
Exomes 𝑓: 0.0000010 ( 0 hom. )

Consequence

ADAMTS2
NM_014244.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.38
Variant links:
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 rank MANE Protein UniProt
ADAMTS2NM_014244.5 linkc.56_70delTGCTGCTGCTGCTGC p.Leu19_Leu23del disruptive_inframe_deletion Exon 1 of 22 ENST00000251582.12 NP_055059.2 O95450-1
ADAMTS2NM_021599.4 linkc.56_70delTGCTGCTGCTGCTGC p.Leu19_Leu23del disruptive_inframe_deletion Exon 1 of 11 NP_067610.1 O95450-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADAMTS2ENST00000251582.12 linkc.56_70delTGCTGCTGCTGCTGC p.Leu19_Leu23del disruptive_inframe_deletion Exon 1 of 22 1 NM_014244.5 ENSP00000251582.7 O95450-1
ADAMTS2ENST00000274609.5 linkc.56_70delTGCTGCTGCTGCTGC p.Leu19_Leu23del disruptive_inframe_deletion Exon 1 of 11 1 ENSP00000274609.5 O95450-2
ADAMTS2ENST00000518335.3 linkc.56_70delTGCTGCTGCTGCTGC p.Leu19_Leu23del disruptive_inframe_deletion Exon 1 of 21 3 ENSP00000489888.2 A0A1B0GTY3
ADAMTS2ENST00000698889.1 linkn.56_70delTGCTGCTGCTGCTGC non_coding_transcript_exon_variant Exon 1 of 21 ENSP00000514008.1 A0A8V8TMU7

Frequencies

GnomAD3 genomes
Cov.:
28
GnomAD4 exome
AF:
0.00000101
AC:
1
AN:
989358
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
472146
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000115
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-178772259; API