rs2307121

Variant names:

• chr5-65329685-C-T
• rs2307121
• NM_197941.4:c.1118-202G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_197941.4(ADAMTS6):​c.1118-202G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,018 control chromosomes in the GnomAD database, including 6,524 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 0.27 (6524 hom., cov: 32)
• Consequence: ADAMTS6 NM_197941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77
• Publications: 20 publications found

Genes affected

ADAMTS6 (HGNC:222): (ADAM metallopeptidase with thrombospondin type 1 motif 6) 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 enzyme. Expression of this gene may be regulated by the cytokine TNF-alpha. [provided by RefSeq, Mar 2016]

ADAMTS6 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_197941.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS6	NM_197941.4	MANE Select	c.1118-202G>A		intron	N/A	NP_922932.2
	ADAMTS6	NR_135689.2		n.1980-202G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS6	ENST00000381055.8	TSL:1 MANE Select	c.1118-202G>A		intron	N/A	ENSP00000370443.3
	ADAMTS6	ENST00000470597.5	TSL:1	n.1139-202G>A		intron	N/A
	ADAMTS6	ENST00000381052.8	TSL:2	n.*244-202G>A		intron	N/A	ENSP00000424377.1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41399 AN: 151900 Hom.: 6527 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.272 AC: 41397 AN: 152018 Hom.: 6524 Cov.: 32 AF XY: 0.274 AC XY: 20327 AN XY: 74294

African (AFR) AF: 0.125 AC: 5179 AN: 41516

American (AMR) AF: 0.283 AC: 4319 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1234 AN: 3468

East Asian (EAS) AF: 0.160 AC: 830 AN: 5182

South Asian (SAS) AF: 0.388 AC: 1870 AN: 4816

European-Finnish (FIN) AF: 0.386 AC: 4068 AN: 10548

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22742 AN: 67936

Other (OTH) AF: 0.260 AC: 548 AN: 2110

Alfa AF: 0.315 Hom.: 33627

Bravo AF: 0.255

Asia WGS AF: 0.259 AC: 901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Benign	0.82
PhyloP100		2.8
Mutation Taster		=98/2	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: rs2307121; hg19: chr5-64625512;