rs407818

Positions:

• chr5-179281208-A-T

Variant summary

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

The NM_014244.5(ADAMTS2):​c.535-8144T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,130 control chromosomes in the GnomAD database, including 12,141 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 0.38 (12141 hom., cov: 33)
• Consequence: ADAMTS2 NM_014244.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS2	NM_014244.5	c.535-8144T>A		intron_variant		ENST00000251582.12	NP_055059.2
ADAMTS2	NM_021599.4	c.535-8144T>A		intron_variant			NP_067610.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS2	ENST00000251582.12	c.535-8144T>A		intron_variant		1	NM_014244.5	ENSP00000251582	P2
ADAMTS2	ENST00000274609.5	c.535-8144T>A		intron_variant		1		ENSP00000274609
ADAMTS2	ENST00000518335.3	c.535-8144T>A		intron_variant		3		ENSP00000489888	A2
ADAMTS2	ENST00000698889.1	c.535-8144T>A		intron_variant, NMD_transcript_variant				ENSP00000514008

Frequencies

GnomAD3 genomes AF: 0.375 AC: 57017 AN: 152010 Hom.: 12131 Cov.: 33

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.375 AC: 57052 AN: 152130 Hom.: 12141 Cov.: 33 AF XY: 0.377 AC XY: 28075 AN XY: 74376

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.388

Alfa AF: 0.416 Hom.: 1975

Bravo AF: 0.357

Asia WGS AF: 0.431 AC: 1496 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.0
DANN	Benign	0.87

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: rs407818; hg19: chr5-178708209;