rs9687070

chr5-179142148-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014244.5(ADAMTS2):c.1630-2113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 151,948 control chromosomes in the GnomAD database, including 30,947 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (30947 hom., cov: 32)
• Consequence: ADAMTS2 NM_014244.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.72

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS2	NM_014244.5	c.1630-2113C>T		intron_variant		ENST00000251582.12
ADAMTS2	XM_047417895.1	c.1135-2113C>T		intron_variant
ADAMTS2	XM_047417896.1	c.748-2113C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS2	ENST00000251582.12	c.1630-2113C>T		intron_variant		1	NM_014244.5	P2
ADAMTS2	ENST00000518335.3	c.1630-2113C>T		intron_variant		3		A2
ADAMTS2	ENST00000698889.1	c.1630-2113C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96726 AN: 151830 Hom.: 30910 Cov.: 32

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.617

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.637 AC: 96827 AN: 151948 Hom.: 30947 Cov.: 32 AF XY: 0.637 AC XY: 47331 AN XY: 74276

Gnomad4 AFR AF: 0.669

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.647

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.613

Alfa AF: 0.638 Hom.: 4457

Bravo AF: 0.639

Asia WGS AF: 0.565 AC: 1967 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.9
Dann	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs9687070; hg19: chr5-178569149; COSMIC: COSV52369359;