chr5-179312015-G-A

Position:

• chr5-179312015-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.534+31752C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,208 control chromosomes in the GnomAD database, including 2,385 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 0.16 (2385 hom., cov: 33)
• Consequence: ADAMTS2 NM_014244.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.859

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 (AMR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS2	NM_014244.5	c.534+31752C>T		intron_variant		ENST00000251582.12	NP_055059.2
ADAMTS2	NM_021599.4	c.534+31752C>T		intron_variant			NP_067610.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS2	ENST00000251582.12	c.534+31752C>T		intron_variant		1	NM_014244.5	ENSP00000251582	P2
ADAMTS2	ENST00000274609.5	c.534+31752C>T		intron_variant		1		ENSP00000274609
ADAMTS2	ENST00000518335.3	c.534+31752C>T		intron_variant		3		ENSP00000489888	A2
ADAMTS2	ENST00000698889.1	c.534+31752C>T		intron_variant, NMD_transcript_variant				ENSP00000514008

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24270 AN: 152090 Hom.: 2383 Cov.: 33

Gnomad AFR AF: 0.0570

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.159 AC: 24274 AN: 152208 Hom.: 2385 Cov.: 33 AF XY: 0.163 AC XY: 12147 AN XY: 74410

Gnomad4 AFR AF: 0.0569

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.170

Alfa AF: 0.180 Hom.: 3547

Bravo AF: 0.167

Asia WGS AF: 0.175 AC: 606 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	0.027
DANN	Benign	0.41

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: rs878933; hg19: chr5-178739016;