Variant 2-200490375-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152387.4(KCTD18):c.1006G>T(p.Gly336Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00336 in 1,614,192 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.019 ( 91 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 64 hom. )

Consequence

KCTD18
NM_152387.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.649

Variant links:

Genes affected

KCTD18 (HGNC:26446): (potassium channel tetramerization domain containing 18) Predicted to be involved in protein homooligomerization. [provided by Alliance of Genome Resources, Apr 2022]

KCTD18 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023891926).

BP6

Variant 2-200490375-C-A is Benign according to our data. Variant chr2-200490375-C-A is described in ClinVar as [Benign]. Clinvar id is 775805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD18	NM_152387.4 linkuse as main transcript	c.1006G>T	p.Gly336Cys	missense_variant	7/7	ENST00000359878.8	NP_689600.2	Q6PI47-1
KCTD18	NM_001321547.2 linkuse as main transcript	c.1006G>T	p.Gly336Cys	missense_variant	7/7		NP_001308476.1	Q6PI47-1A8K4A2
KCTD18	NM_001321548.2 linkuse as main transcript	c.379G>T	p.Gly127Cys	missense_variant	7/7		NP_001308477.1
KCTD18	NM_001321550.2 linkuse as main transcript	c.379G>T	p.Gly127Cys	missense_variant	7/7		NP_001308479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD18	ENST00000359878.8 linkuse as main transcript	c.1006G>T	p.Gly336Cys	missense_variant	7/7	1	NM_152387.4	ENSP00000352941.3		Q6PI47-1
KCTD18	ENST00000409157.5 linkuse as main transcript	c.1006G>T	p.Gly336Cys	missense_variant	7/7	1		ENSP00000386751.1		Q6PI47-1

Frequencies

GnomAD3 genomes

AF:

0.0187

AC:

2853

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0629

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0143

GnomAD3 exomes

AF:

0.00503

AC:

1263

AN:

251280

Hom.:

AF XY:

0.00389

AC XY:

529

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.0657

Gnomad AMR exome

AF:

0.00437

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00174

AC:

2549

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

1075

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0584

Gnomad4 AMR exome

AF:

0.00512

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000106

Gnomad4 OTH exome

AF:

0.00373

GnomAD4 genome

AF:

0.0188

AC:

2867

AN:

152334

Hom.:

Cov.:

AF XY:

0.0182

AC XY:

1358

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0631

Gnomad4 AMR

AF:

0.0131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00218

Hom.:

Bravo

AF:

0.0208

ESP6500AA

AF:

0.0615

AC:

271

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00624

AC:

758

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

KCTD18-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 12, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.00086

T;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.49

.;T

MetaRNN

Benign

0.0024

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.18

N;N

REVEL

Benign

0.096

Sift

Benign

0.15

T;T

Sift4G

Uncertain

0.031

D;D

Polyphen

0.0040

B;B

Vest4

0.081

MVP

0.45

MPC

0.24

ClinPred

0.0061

GERP RS

2.8

Varity_R

0.092

gMVP

0.19

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over