5-179345258-GGCAGCAGCAGCA-GGCA

Position:

• chr5-179345258-GGCAGCAGCAGCA-GGCA

Variant summary

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

The NM_014244.5(ADAMTS2):​c.62_70del​(p.Leu21_Leu23del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 989,342 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: 0.000010 (0 hom.)
• Consequence: ADAMTS2 NM_014244.5 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.38

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 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.62_70del	p.Leu21_Leu23del	inframe_deletion	1/22	ENST00000251582.12	NP_055059.2
ADAMTS2	NM_021599.4	c.62_70del	p.Leu21_Leu23del	inframe_deletion	1/11		NP_067610.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS2	ENST00000251582.12	c.62_70del	p.Leu21_Leu23del	inframe_deletion	1/22	1	NM_014244.5	ENSP00000251582	P2
ADAMTS2	ENST00000274609.5	c.62_70del	p.Leu21_Leu23del	inframe_deletion	1/11	1		ENSP00000274609
ADAMTS2	ENST00000518335.3	c.62_70del	p.Leu21_Leu23del	inframe_deletion	1/21	3		ENSP00000489888	A2
ADAMTS2	ENST00000698889.1	c.62_70del	p.Leu21_Leu23del	inframe_deletion, NMD_transcript_variant	1/21			ENSP00000514008

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.0000101 AC: 10 AN: 989342 Hom.: 0 AF XY: 0.00000635 AC XY: 3 AN XY: 472138

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: 0.0000115

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

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

LitVar

Other links and lift over

dbSNP: rs568040559; hg19: chr5-178772259;