chr5-179110916-C-T

Variant names:

• chr5-179110916-C-T
• rs1044205
• NM_014244.5:c.*2951G>A

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.*2951G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 151,976 control chromosomes in the GnomAD database, including 5,392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (5392 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADAMTS2 NM_014244.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0490
• Publications: 3 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=-0.71).
• BP6: Variant 5-179110916-C-T is Benign according to our data. Variant chr5-179110916-C-T is described in ClinVar as Benign. ClinVar VariationId is 353036.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.359 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.*2951G>A		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.*2951G>A		3_prime_UTR	Exon 22 of 22	ENSP00000251582.7	O95450-1
	ADAMTS2	ENST00000957641.1		c.*2951G>A		3_prime_UTR	Exon 22 of 22	ENSP00000627700.1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37274 AN: 151858 Hom.: 5390 Cov.: 33

Gnomad AFR AF: 0.0811

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.278

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

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: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.245 AC: 37284 AN: 151976 Hom.: 5392 Cov.: 33 AF XY: 0.248 AC XY: 18418 AN XY: 74270

African (AFR) AF: 0.0812 AC: 3373 AN: 41534

American (AMR) AF: 0.352 AC: 5377 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1104 AN: 3466

East Asian (EAS) AF: 0.316 AC: 1624 AN: 5138

South Asian (SAS) AF: 0.374 AC: 1799 AN: 4814

European-Finnish (FIN) AF: 0.282 AC: 2972 AN: 10522

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19959 AN: 67918

Other (OTH) AF: 0.275 AC: 580 AN: 2112

Alfa AF: 0.277 Hom.: 2147

Bravo AF: 0.244

Asia WGS AF: 0.314 AC: 1095 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	-0.71
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		0.049
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: rs1044205; hg19: chr5-178537917;