rs2086452

Variant names:

• chr15-100188458-G-A
• rs2086452
• NM_139057.4:c.1181+10860C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-100188458-G-A
• chr15-100188458-G-C

Variant summary

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

The NM_139057.4(ADAMTS17):​c.1181+10860C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 151,738 control chromosomes in the GnomAD database, including 22,910 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 0.54 (22910 hom., cov: 31)
• Consequence: ADAMTS17 NM_139057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145
• Publications: 10 publications found

Genes affected

ADAMTS17 (HGNC:17109): (ADAM metallopeptidase with thrombospondin type 1 motif 17) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. ADAMTS family members 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 protein, which may promote breast cancer cell growth and survival. Mutations in this gene are associated with a Weill-Marchesani-like syndrome, which is characterized by lenticular myopia, ectopia lentis, glaucoma, spherophakia, and short stature. [provided by RefSeq, May 2016]

ADAMTS17 Gene-Disease associations (from GenCC):

• Weill-Marchesani 4 syndrome, recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P, Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS17	NM_139057.4	c.1181+10860C>T		intron_variant	Intron 8 of 21	ENST00000268070.9	NP_620688.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS17	ENST00000268070.9	c.1181+10860C>T		intron_variant	Intron 8 of 21	1	NM_139057.4	ENSP00000268070.4
ADAMTS17	ENST00000568565.2	c.1181+10860C>T		intron_variant	Intron 8 of 22	5		ENSP00000456161.2
ADAMTS17	ENST00000378898.8	n.862+10860C>T		intron_variant	Intron 7 of 14	2
ADAMTS17	ENST00000559976.1	n.177+10860C>T		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82375 AN: 151622 Hom.: 22886 Cov.: 31

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.543 AC: 82462 AN: 151738 Hom.: 22910 Cov.: 31 AF XY: 0.545 AC XY: 40400 AN XY: 74144

African (AFR) AF: 0.444 AC: 18368 AN: 41374

American (AMR) AF: 0.568 AC: 8658 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1868 AN: 3472

East Asian (EAS) AF: 0.484 AC: 2495 AN: 5156

South Asian (SAS) AF: 0.376 AC: 1813 AN: 4816

European-Finnish (FIN) AF: 0.645 AC: 6743 AN: 10460

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40638 AN: 67888

Other (OTH) AF: 0.550 AC: 1161 AN: 2110

Alfa AF: 0.584 Hom.: 46949

Bravo AF: 0.543

Asia WGS AF: 0.471 AC: 1635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.61
PhyloP100		-0.14
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: rs2086452; hg19: chr15-100728663;