dbSNP rs770212030: ADAMTS2:p.Pro32_Pro34del (chr5-179345227-GGGCGGCGGC-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3

The NM_014244.5(ADAMTS2):c.93_101delGCCGCCGCC(p.Pro32_Pro34del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 971,256 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P31P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ADAMTS2
NM_014244.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.24

Publications

0 publications found

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]

ADAMTS2 Gene-Disease associations (from GenCC):

Ehlers-Danlos syndrome, dermatosparaxis type
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, G2P, PanelApp Australia, Illumina

ADAMTS2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP3

Nonframeshift variant in repetitive region in NM_014244.5

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014244.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS2	NM_014244.5	MANE Select	c.93_101delGCCGCCGCC	p.Pro32_Pro34del	disruptive_inframe_deletion	Exon 1 of 22	NP_055059.2
	ADAMTS2	NM_021599.4		c.93_101delGCCGCCGCC	p.Pro32_Pro34del	disruptive_inframe_deletion	Exon 1 of 11	NP_067610.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ADAMTS2	ENST00000251582.12	TSL:1 MANE Select	c.93_101delGCCGCCGCC	p.Pro32_Pro34del	disruptive_inframe_deletion	Exon 1 of 22	ENSP00000251582.7
ADAMTS2	ENST00000274609.5	TSL:1	c.93_101delGCCGCCGCC	p.Pro32_Pro34del	disruptive_inframe_deletion	Exon 1 of 11	ENSP00000274609.5
ADAMTS2	ENST00000518335.3	TSL:3	c.93_101delGCCGCCGCC	p.Pro32_Pro34del	disruptive_inframe_deletion	Exon 1 of 21	ENSP00000489888.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

971256

Hom.:

AF XY:

0.00000432

AC XY:

AN XY:

463414

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18936

American (AMR)

AF:

0.00

AC:

AN:

5112

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9396

East Asian (EAS)

AF:

0.00

AC:

AN:

14578

South Asian (SAS)

AF:

0.00

AC:

AN:

18548

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2390

European-Non Finnish (NFE)

AF:

0.00000235

AC:

AN:

852000

Other (OTH)

AF:

0.00

AC:

AN:

35910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.2

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over