NM_014244.5:c.1630-2113C>T

Variant names:

• chr5-179142148-G-A
• rs9687070
• NM_014244.5:c.1630-2113C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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), G2P, Orphanet, Illumina, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS2	NM_014244.5	MANE Select	c.1630-2113C>T		intron	N/A	NP_055059.2	O95450-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS2	ENST00000251582.12	TSL:1 MANE Select	c.1630-2113C>T		intron	N/A	ENSP00000251582.7	O95450-1
	ADAMTS2	ENST00000957641.1		c.1630-2113C>T		intron	N/A	ENSP00000627700.1
	ADAMTS2	ENST00000518335.3	TSL:3	c.1630-2113C>T		intron	N/A	ENSP00000489888.2	A0A1B0GTY3

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

African (AFR) AF: 0.669 AC: 27708 AN: 41402

American (AMR) AF: 0.639 AC: 9743 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2353 AN: 3472

East Asian (EAS) AF: 0.570 AC: 2948 AN: 5170

South Asian (SAS) AF: 0.647 AC: 3102 AN: 4798

European-Finnish (FIN) AF: 0.615 AC: 6499 AN: 10572

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42438 AN: 67958

Other (OTH) AF: 0.613 AC: 1295 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.46
PhyloP100		-3.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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