15-100125032-T-C

Variant names:

• chr15-100125032-T-C
• rs2086455
• NM_139057.4:c.1721+6975A>G

Variant summary

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

The NM_139057.4(ADAMTS17):​c.1721+6975A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 152,284 control chromosomes in the GnomAD database, including 62,200 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 0.90 (62200 hom., cov: 33)
• Consequence: ADAMTS17 NM_139057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139057.4. 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
	ADAMTS17	NM_139057.4	MANE Select	c.1721+6975A>G		intron	N/A	NP_620688.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS17	ENST00000268070.9	TSL:1 MANE Select	c.1721+6975A>G		intron	N/A	ENSP00000268070.4
	ADAMTS17	ENST00000961098.1		c.1721+6975A>G		intron	N/A	ENSP00000631157.1
	ADAMTS17	ENST00000568565.2	TSL:5	c.1721+6975A>G		intron	N/A	ENSP00000456161.2

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136807 AN: 152166 Hom.: 62160 Cov.: 33

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.943

Gnomad ASJ AF: 0.945

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.873

Gnomad FIN AF: 0.970

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.964

Gnomad OTH AF: 0.914

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

GnomAD4 genome AF: 0.899 AC: 136903 AN: 152284 Hom.: 62200 Cov.: 33 AF XY: 0.899 AC XY: 66948 AN XY: 74456

African (AFR) AF: 0.758 AC: 31471 AN: 41540

American (AMR) AF: 0.943 AC: 14427 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.945 AC: 3280 AN: 3472

East Asian (EAS) AF: 0.883 AC: 4554 AN: 5160

South Asian (SAS) AF: 0.874 AC: 4218 AN: 4826

European-Finnish (FIN) AF: 0.970 AC: 10300 AN: 10620

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.964 AC: 65615 AN: 68042

Other (OTH) AF: 0.914 AC: 1934 AN: 2116

Alfa AF: 0.935 Hom.: 119628

Bravo AF: 0.891

Asia WGS AF: 0.895 AC: 3115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.37
PhyloP100		0.039
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: rs2086455; hg19: chr15-100665237;