rs78886769

Variant names:

• chr5-179111428-G-A
• rs78886769
• NM_014244.5:c.*2439C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-179111428-G-A
• chr5-179111428-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014244.5(ADAMTS2):​c.*2439C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0407 in 152,380 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.041 (167 hom., cov: 33)
  • Exomes 𝑓: 0.045 (0 hom.)
• Consequence: ADAMTS2 NM_014244.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.289
• Publications: 1 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), G2P, Orphanet, Illumina, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-179111428-G-A is Benign according to our data. Variant chr5-179111428-G-A is described in ClinVar as Benign. ClinVar VariationId is 353047.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0604 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014244.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS2	NM_014244.5	MANE Select	c.*2439C>T		3_prime_UTR	Exon 22 of 22	NP_055059.2	O95450-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS2	ENST00000251582.12	TSL:1 MANE Select	c.*2439C>T		3_prime_UTR	Exon 22 of 22	ENSP00000251582.7	O95450-1
	ADAMTS2	ENST00000957641.1		c.*2439C>T		3_prime_UTR	Exon 22 of 22	ENSP00000627700.1

Frequencies

GnomAD3 genomes AF: 0.0407 AC: 6201 AN: 152218 Hom.: 168 Cov.: 33

Gnomad AFR AF: 0.00914

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0476

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00806

Gnomad FIN AF: 0.0434

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0620

Gnomad OTH AF: 0.0487

GnomAD4 exome AF: 0.0455 AC: 2 AN: 44 Hom.: 0 Cov.: 0 AF XY: 0.0625 AC XY: 2 AN XY: 32

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0526 AC: 2 AN: 38

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0407 AC: 6199 AN: 152336 Hom.: 167 Cov.: 33 AF XY: 0.0381 AC XY: 2838 AN XY: 74490

African (AFR) AF: 0.00912 AC: 379 AN: 41574

American (AMR) AF: 0.0475 AC: 726 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 162 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.00807 AC: 39 AN: 4832

European-Finnish (FIN) AF: 0.0434 AC: 461 AN: 10618

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0620 AC: 4218 AN: 68036

Other (OTH) AF: 0.0482 AC: 102 AN: 2116

Alfa AF: 0.0394 Hom.: 39

Bravo AF: 0.0405

Asia WGS AF: 0.00722 AC: 26 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Ehlers-Danlos syndrome, dermatosparaxis type (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.66
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism

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: rs78886769; hg19: chr5-178538429;