rs770212030

Variant names:

• chr5-179345227-GGGCGGCGGC-G
• NM_014244.5:c.93_101delGCCGCCGCC

Your query was ambiguous. Multiple possible variants found:

• chr5-179345227-GGGCGGCGGC-G
• chr5-179345227-GGGCGGCGGC-GGGC
• chr5-179345227-GGGCGGCGGC-GGGCGGC
• chr5-179345227-GGGCGGCGGC-GGGCGGCGGCGGC
• chr5-179345227-GGGCGGCGGC-GGGCGGCGGCGGCGGC
• chr5-179345227-GGGCGGCGGC-GGGCGGCGGCGGCGGCGGC

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP3

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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ADAMTS2 NM_014244.5 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.24

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_014244.5

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS2	NM_014244.5	c.93_101delGCCGCCGCC	p.Pro32_Pro34del	disruptive_inframe_deletion	Exon 1 of 22	ENST00000251582.12	NP_055059.2
ADAMTS2	NM_021599.4	c.93_101delGCCGCCGCC	p.Pro32_Pro34del	disruptive_inframe_deletion	Exon 1 of 11		NP_067610.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS2	ENST00000251582.12	c.93_101delGCCGCCGCC	p.Pro32_Pro34del	disruptive_inframe_deletion	Exon 1 of 22	1	NM_014244.5	ENSP00000251582.7
ADAMTS2	ENST00000274609.5	c.93_101delGCCGCCGCC	p.Pro32_Pro34del	disruptive_inframe_deletion	Exon 1 of 11	1		ENSP00000274609.5
ADAMTS2	ENST00000518335.3	c.93_101delGCCGCCGCC	p.Pro32_Pro34del	disruptive_inframe_deletion	Exon 1 of 21	3		ENSP00000489888.2
ADAMTS2	ENST00000698889.1	n.93_101delGCCGCCGCC		non_coding_transcript_exon_variant	Exon 1 of 21			ENSP00000514008.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 2 AN: 971256 Hom.: 0 AF XY: 0.00000432 AC XY: 2 AN XY: 463414

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: 0.00000235

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: chr5-178772228;