Variant 17-75047300-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015353.3(KCTD2):c.50G>T(p.Gly17Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000663 in 150,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Consequence

KCTD2
NM_015353.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.42

Variant links:

Genes affected

KCTD2 (HGNC:21294): (potassium channel tetramerization domain containing 2) Predicted to enable cullin family protein binding activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Predicted to be part of Cul3-RING ubiquitin ligase complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

KCTD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35531235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KCTD2	NM_015353.3 linkuse as main transcript	c.50G>T	p.Gly17Val	missense_variant	1/6	ENST00000322444.7
KCTD2	NR_110834.2 linkuse as main transcript	n.75+1G>T		splice_donor_variant, non_coding_transcript_variant
KCTD2	NR_110835.2 linkuse as main transcript	n.366-1920G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD2	ENST00000322444.7 linkuse as main transcript	c.50G>T	p.Gly17Val	missense_variant	1/6	1	NM_015353.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150806

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000663

AC:

AN:

150806

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73632

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 22, 2023

The c.50G>T (p.G17V) alteration is located in exon 1 (coding exon 1) of the KCTD2 gene. This alteration results from a G to T substitution at nucleotide position 50, causing the glycine (G) at amino acid position 17 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.049

BayesDel_noAF

Benign

-0.17

Cadd

Pathogenic

Dann

Uncertain

0.99

DEOGEN2

Benign

0.0074

Eigen

Benign

-0.054

Eigen_PC

Benign

-0.028

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.56

M_CAP

Pathogenic

0.85

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.79

REVEL

Benign

0.12

Sift

Uncertain

0.029

Sift4G

Benign

0.26

Polyphen

0.65

Vest4

0.27

MutPred

0.41

Gain of sheet (P = 0.0266);

MVP

0.65

MPC

1.3

ClinPred

0.73

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.16

gMVP

0.40

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