NM_014244.5:c.1516-492G>A

Variant names:

• chr5-179152747-C-T
• rs3776817
• NM_014244.5:c.1516-492G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014244.5(ADAMTS2):​c.1516-492G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 151,882 control chromosomes in the GnomAD database, including 6,288 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 0.28 (6288 hom., cov: 32)
• Consequence: ADAMTS2 NM_014244.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• 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), Genomics England PanelApp, Orphanet, G2P, PanelApp Australia, Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.348 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS2	NM_014244.5	MANE Select	c.1516-492G>A		intron	N/A	NP_055059.2
	ADAMTS2	NM_021599.4		c.1516-492G>A		intron	N/A	NP_067610.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS2	ENST00000251582.12	TSL:1 MANE Select	c.1516-492G>A		intron	N/A	ENSP00000251582.7
	ADAMTS2	ENST00000274609.5	TSL:1	c.1516-492G>A		intron	N/A	ENSP00000274609.5
	ADAMTS2	ENST00000518335.3	TSL:3	c.1516-492G>A		intron	N/A	ENSP00000489888.2

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43178 AN: 151764 Hom.: 6268 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.285 AC: 43236 AN: 151882 Hom.: 6288 Cov.: 32 AF XY: 0.286 AC XY: 21241 AN XY: 74218

African (AFR) AF: 0.353 AC: 14620 AN: 41426

American (AMR) AF: 0.313 AC: 4780 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 865 AN: 3462

East Asian (EAS) AF: 0.326 AC: 1669 AN: 5116

South Asian (SAS) AF: 0.309 AC: 1485 AN: 4810

European-Finnish (FIN) AF: 0.250 AC: 2644 AN: 10556

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16169 AN: 67936

Other (OTH) AF: 0.289 AC: 609 AN: 2104

Alfa AF: 0.258 Hom.: 3576

Bravo AF: 0.295

Asia WGS AF: 0.303 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.56
PhyloP100		-1.9
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: rs3776817; hg19: chr5-178579748;