5-179263724-G-A

Position:

• chr5-179263724-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.688+9187C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 152,106 control chromosomes in the GnomAD database, including 19,321 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 0.50 (19321 hom., cov: 33)
• Consequence: ADAMTS2 NM_014244.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS2	NM_014244.5	c.688+9187C>T		intron_variant		ENST00000251582.12	NP_055059.2
ADAMTS2	XM_047417896.1	c.-4723C>T		5_prime_UTR_variant	1/20		XP_047273852.1
ADAMTS2	NM_021599.4	c.688+9187C>T		intron_variant			NP_067610.1
ADAMTS2	XM_047417895.1	c.193+9187C>T		intron_variant			XP_047273851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS2	ENST00000251582.12	c.688+9187C>T		intron_variant		1	NM_014244.5	ENSP00000251582	P2
ADAMTS2	ENST00000274609.5	c.688+9187C>T		intron_variant		1		ENSP00000274609
ADAMTS2	ENST00000518335.3	c.688+9187C>T		intron_variant		3		ENSP00000489888	A2
ADAMTS2	ENST00000698889.1	c.688+9187C>T		intron_variant, NMD_transcript_variant				ENSP00000514008

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76263 AN: 151988 Hom.: 19292 Cov.: 33

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.497

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

GnomAD4 genome AF: 0.502 AC: 76336 AN: 152106 Hom.: 19321 Cov.: 33 AF XY: 0.499 AC XY: 37120 AN XY: 74362

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.501

Alfa AF: 0.496 Hom.: 6466

Bravo AF: 0.506

Asia WGS AF: 0.627 AC: 2181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.71

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: rs338882; hg19: chr5-178690725;