Variant 2-200490212-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_152387.4(KCTD18):c.1169G>C(p.Cys390Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,613,828 control chromosomes in the GnomAD database, including 119,506 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.34 ( 9126 hom., cov: 34)

Exomes 𝑓: 0.39 ( 110380 hom. )

Consequence

KCTD18
NM_152387.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.48

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012983084).

BP6

Variant 2-200490212-C-G is Benign according to our data. Variant chr2-200490212-C-G is described in ClinVar as [Benign]. Clinvar id is 3059758.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KCTD18	NM_152387.4 linkuse as main transcript	c.1169G>C	p.Cys390Ser	missense_variant	7/7	ENST00000359878.8	NP_689600.2
KCTD18	NM_001321547.2 linkuse as main transcript	c.1169G>C	p.Cys390Ser	missense_variant	7/7		NP_001308476.1
KCTD18	NM_001321548.2 linkuse as main transcript	c.542G>C	p.Cys181Ser	missense_variant	7/7		NP_001308477.1
KCTD18	NM_001321550.2 linkuse as main transcript	c.542G>C	p.Cys181Ser	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.1169G>C	p.Cys390Ser	missense_variant	7/7	1	NM_152387.4	ENSP00000352941	P1	Q6PI47-1
KCTD18	ENST00000409157.5 linkuse as main transcript	c.1169G>C	p.Cys390Ser	missense_variant	7/7	1		ENSP00000386751	P1	Q6PI47-1

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

51444

AN:

152112

Hom.:

9123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.345

Gnomad AMR

AF:

0.386

Gnomad ASJ

AF:

0.383

Gnomad EAS

AF:

0.444

Gnomad SAS

AF:

0.331

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.395

Gnomad NFE

AF:

0.391

Gnomad OTH

AF:

0.349

GnomAD3 exomes

AF:

0.370

AC:

92954

AN:

251146

Hom.:

17580

AF XY:

0.370

AC XY:

50237

AN XY:

135764

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.391

Gnomad ASJ exome

AF:

0.380

Gnomad EAS exome

AF:

0.436

Gnomad SAS exome

AF:

0.337

Gnomad FIN exome

AF:

0.322

Gnomad NFE exome

AF:

0.391

Gnomad OTH exome

AF:

0.384

GnomAD4 exome

AF:

0.386

AC:

563895

AN:

1461598

Hom.:

110380

Cov.:

AF XY:

0.385

AC XY:

279971

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.212

Gnomad4 AMR exome

AF:

0.388

Gnomad4 ASJ exome

AF:

0.375

Gnomad4 EAS exome

AF:

0.472

Gnomad4 SAS exome

AF:

0.338

Gnomad4 FIN exome

AF:

0.317

Gnomad4 NFE exome

AF:

0.395

Gnomad4 OTH exome

AF:

0.382

GnomAD4 genome

AF:

0.338

AC:

51471

AN:

152230

Hom.:

9126

Cov.:

AF XY:

0.336

AC XY:

25004

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.224

Gnomad4 AMR

AF:

0.386

Gnomad4 ASJ

AF:

0.383

Gnomad4 EAS

AF:

0.444

Gnomad4 SAS

AF:

0.330

Gnomad4 FIN

AF:

0.308

Gnomad4 NFE

AF:

0.391

Gnomad4 OTH

AF:

0.347

Alfa

AF:

0.387

Hom.:

8890

Bravo

AF:

0.340

TwinsUK

AF:

0.391

AC:

1448

ALSPAC

AF:

0.383

AC:

1478

ESP6500AA

AF:

0.223

AC:

982

ESP6500EA

AF:

0.395

AC:

3397

ExAC

AF:

0.366

AC:

44402

Asia WGS

AF:

0.384

AC:

1336

AN:

3478

EpiCase

AF:

0.396

EpiControl

AF:

0.391

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KCTD18-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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

0.051

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.0

DANN

Benign

0.25

DEOGEN2

Benign

0.00077

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00049

LIST_S2

Benign

0.16

.;T

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-2.0

N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.38

PROVEAN

Benign

0.84

N;N

REVEL

Benign

0.050

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.010

MutPred

0.075

Gain of glycosylation at C390 (P = 0.0029);Gain of glycosylation at C390 (P = 0.0029);

MPC

0.24

ClinPred

0.0013

GERP RS

3.1

Varity_R

0.035

gMVP

0.15

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