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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00
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/exons MANE Protein UniProt
ADAMTS2NM_014244.5 linkc.53_70dupTGCTGCTGCTGCTGCTGC p.Leu18_Leu23dup conservative_inframe_insertion 1/22 ENST00000251582.12 NP_055059.2 O95450-1
ADAMTS2NM_021599.4 linkc.53_70dupTGCTGCTGCTGCTGCTGC p.Leu18_Leu23dup conservative_inframe_insertion 1/11 NP_067610.1 O95450-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ADAMTS2ENST00000251582.12 linkc.53_70dupTGCTGCTGCTGCTGCTGC p.Leu18_Leu23dup conservative_inframe_insertion 1/221 NM_014244.5 ENSP00000251582.7 O95450-1
ADAMTS2ENST00000274609.5 linkc.53_70dupTGCTGCTGCTGCTGCTGC p.Leu18_Leu23dup conservative_inframe_insertion 1/111 ENSP00000274609.5 O95450-2
ADAMTS2ENST00000518335.3 linkc.53_70dupTGCTGCTGCTGCTGCTGC p.Leu18_Leu23dup conservative_inframe_insertion 1/213 ENSP00000489888.2 A0A1B0GTY3
ADAMTS2ENST00000698889.1 linkn.53_70dupTGCTGCTGCTGCTGCTGC non_coding_transcript_exon_variant 1/21 ENSP00000514008.1 A0A8V8TMU7

Frequencies

GnomAD3 genomes
AF:
0.0000204
AC:
3
AN:
146980
Hom.:
0
Cov.:
28
show subpopulations
Gnomad AFR
AF:
0.0000500
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000209
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000404
AC:
4
AN:
989358
Hom.:
0
Cov.:
29
AF XY:
0.00000212
AC XY:
1
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:
0.000126
Gnomad4 SAS exome
AF:
0.000106
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000204
AC:
3
AN:
146980
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
71540
show subpopulations
Gnomad4 AFR
AF:
0.0000500
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000209
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs568040559; hg19: chr5-178772259; API