rs2235320

Positions:

• chr22-37057216-G-T

Variant summary

Our verdict is Benign. Variant got -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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
KCTD17	NM_001282684.2	c.391-182G>T		intron_variant		ENST00000403888.8	NP_001269613.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD17	ENST00000403888.8	c.391-182G>T		intron_variant		1	NM_001282684.2	ENSP00000385096	A2

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

Gnomad4 AFR AF: 0.0254

Gnomad4 AMR AF: 0.0744

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.0997

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.103

Alfa AF: 0.125 Hom.: 1678

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 05, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.2
DANN	Benign	0.69

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

LitVar

Other links and lift over

dbSNP: rs2235320; hg19: chr22-37453256;