chr5-179147867-A-G

Variant names:

• chr5-179147867-A-G
• rs3776816
• NM_014244.5:c.1629+4275T>C

Variant summary

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

The NM_014244.5(ADAMTS2):​c.1629+4275T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 152,080 control chromosomes in the GnomAD database, including 29,246 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 0.62 (29246 hom., cov: 32)
• Consequence: ADAMTS2 NM_014244.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS2	NM_014244.5	c.1629+4275T>C		intron_variant	Intron 10 of 21	ENST00000251582.12	NP_055059.2
ADAMTS2	XM_047417895.1	c.1134+4275T>C		intron_variant	Intron 9 of 20		XP_047273851.1
ADAMTS2	XM_047417896.1	c.747+4275T>C		intron_variant	Intron 8 of 19		XP_047273852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS2	ENST00000251582.12	c.1629+4275T>C		intron_variant	Intron 10 of 21	1	NM_014244.5	ENSP00000251582.7
ADAMTS2	ENST00000518335.3	c.1629+4275T>C		intron_variant	Intron 10 of 20	3		ENSP00000489888.2
ADAMTS2	ENST00000698889.1	n.1629+4275T>C		intron_variant	Intron 10 of 20			ENSP00000514008.1

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94133 AN: 151962 Hom.: 29216 Cov.: 32

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.620 AC: 94224 AN: 152080 Hom.: 29246 Cov.: 32 AF XY: 0.620 AC XY: 46114 AN XY: 74324

African (AFR) AF: 0.607 AC: 25188 AN: 41476

American (AMR) AF: 0.634 AC: 9709 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2348 AN: 3470

East Asian (EAS) AF: 0.569 AC: 2939 AN: 5164

South Asian (SAS) AF: 0.647 AC: 3115 AN: 4818

European-Finnish (FIN) AF: 0.615 AC: 6484 AN: 10540

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42430 AN: 67988

Other (OTH) AF: 0.601 AC: 1271 AN: 2116

Alfa AF: 0.622 Hom.: 11940

Bravo AF: 0.619

Asia WGS AF: 0.562 AC: 1957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.46
PhyloP100		0.079
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: rs3776816; hg19: chr5-178574868; COSMIC: COSV51108416; COSMIC: COSV51108416;