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

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]

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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD17	NM_001282684.2	c.391-182G>T		intron_variant	Intron 3 of 8	ENST00000403888.8	NP_001269613.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD17	ENST00000403888.8	c.391-182G>T		intron_variant	Intron 3 of 8	1	NM_001282684.2	ENSP00000385096.4

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Other links and lift over

dbSNP: rs2235320; hg19: chr22-37453256; COSMIC: COSV107455683; COSMIC: COSV107455683;