rs2235320

Variant names:

• chr22-37057216-G-T
• rs2235320
• NM_001282684.2:c.391-182G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001282684.2(KCTD17):​c.391-182G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0957 in 152,268 control chromosomes in the GnomAD database, including 875 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.096 (875 hom., cov: 32)
• Consequence: KCTD17 NM_001282684.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.721
• Publications: 12 publications found

Genes affected

KCTD17 (HGNC:25705): (potassium channel tetramerization domain containing 17) This gene encodes a protein that belongs to a conserved family of potassium channel tetramerization domain (KCTD)-containing proteins. The encoded protein functions in ciliogenesis by acting as a substrate adaptor for the cullin3-based ubiquitin-conjugating enzyme E3 ligase, and targets trichoplein, a keratin-binding protein, for degradation via polyubiquitinylation. A mutation in this gene is associated with autosomal dominant myoclonic dystonia 26. [provided by RefSeq, Nov 2016]

KCTD17 Gene-Disease associations (from GenCC):

• myoclonic dystonia 26

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• myoclonus-dystonia syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 22-37057216-G-T is Benign according to our data. Variant chr22-37057216-G-T is described in ClinVar as Benign. ClinVar VariationId is 1175421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282684.2. 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
	KCTD17	NM_001282684.2	MANE Select	c.391-182G>T		intron	N/A	NP_001269613.2	Q8N5Z5-1
	KCTD17	NM_024681.4		c.391-182G>T		intron	N/A	NP_078957.3	Q8N5Z5-2
	KCTD17	NM_001282685.2		c.391-182G>T		intron	N/A	NP_001269614.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD17	ENST00000403888.8	TSL:1 MANE Select	c.391-182G>T		intron	N/A	ENSP00000385096.4	Q8N5Z5-1
	KCTD17	ENST00000402077.8	TSL:1	c.391-182G>T		intron	N/A	ENSP00000384391.4	Q8N5Z5-2
	KCTD17	ENST00000851347.1		c.391-182G>T		intron	N/A	ENSP00000521406.1

Frequencies

GnomAD3 genomes AF: 0.0958 AC: 14572 AN: 152150 Hom.: 872 Cov.: 32

Gnomad AFR AF: 0.0255

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0747

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0997

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.0957 AC: 14572 AN: 152268 Hom.: 875 Cov.: 32 AF XY: 0.0976 AC XY: 7270 AN XY: 74454

African (AFR) AF: 0.0254 AC: 1056 AN: 41566

American (AMR) AF: 0.0744 AC: 1138 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 526 AN: 3472

East Asian (EAS) AF: 0.0997 AC: 516 AN: 5176

South Asian (SAS) AF: 0.145 AC: 700 AN: 4826

European-Finnish (FIN) AF: 0.145 AC: 1542 AN: 10612

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8809 AN: 68000

Other (OTH) AF: 0.103 AC: 217 AN: 2112

Alfa AF: 0.119 Hom.: 2282

Bravo AF: 0.0864

Asia WGS AF: 0.115 AC: 402 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.2
DANN	Benign	0.69
PhyloP100		0.72
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2235320; hg19: chr22-37453256; COSMIC: COSV107455683; COSMIC: COSV107455683;