chr5-179272310-C-T

Variant names:

• chr5-179272310-C-T
• rs901254
• NM_014244.5:c.688+601G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014244.5(ADAMTS2):​c.688+601G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 152,294 control chromosomes in the GnomAD database, including 131 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 0.027 (131 hom., cov: 33)
• Consequence: ADAMTS2 NM_014244.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166
• Publications: 5 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=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0273 (4151/152294) while in subpopulation NFE AF = 0.0339 (2304/68024). AF 95% confidence interval is 0.0327. There are 131 homozygotes in GnomAd4. There are 2245 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 131 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS2	NM_014244.5	c.688+601G>A		intron_variant	Intron 3 of 21	ENST00000251582.12	NP_055059.2
ADAMTS2	NM_021599.4	c.688+601G>A		intron_variant	Intron 3 of 10		NP_067610.1
ADAMTS2	XM_047417895.1	c.193+601G>A		intron_variant	Intron 2 of 20		XP_047273851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS2	ENST00000251582.12	c.688+601G>A		intron_variant	Intron 3 of 21	1	NM_014244.5	ENSP00000251582.7
ADAMTS2	ENST00000274609.5	c.688+601G>A		intron_variant	Intron 3 of 10	1		ENSP00000274609.5
ADAMTS2	ENST00000518335.3	c.688+601G>A		intron_variant	Intron 3 of 20	3		ENSP00000489888.2
ADAMTS2	ENST00000698889.1	n.688+601G>A		intron_variant	Intron 3 of 20			ENSP00000514008.1

Frequencies

GnomAD3 genomes AF: 0.0273 AC: 4151 AN: 152176 Hom.: 131 Cov.: 33

Gnomad AFR AF: 0.00605

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0125

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00643

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0339

Gnomad OTH AF: 0.0168

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

GnomAD4 genome AF: 0.0273 AC: 4151 AN: 152294 Hom.: 131 Cov.: 33 AF XY: 0.0302 AC XY: 2245 AN XY: 74452

African (AFR) AF: 0.00604 AC: 251 AN: 41576

American (AMR) AF: 0.0125 AC: 191 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5174

South Asian (SAS) AF: 0.00644 AC: 31 AN: 4816

European-Finnish (FIN) AF: 0.122 AC: 1292 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0339 AC: 2304 AN: 68024

Other (OTH) AF: 0.0166 AC: 35 AN: 2110

Alfa AF: 0.0298 Hom.: 199

Bravo AF: 0.0186

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.95
PhyloP100		0.17
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: rs901254; hg19: chr5-178699311;