Variant 17-75047393-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015353.3(KCTD2):c.143C>T(p.Ala48Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 1,153,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

KCTD2
NM_015353.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.183

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14449656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD2	NM_015353.3 link	c.143C>T	p.Ala48Val	missense_variant	1/6	ENST00000322444.7	NP_056168.1	Q14681Q8IYY2
KCTD2	NR_110834.2 link	n.76-26C>T		intron_variant
KCTD2	NR_110835.2 link	n.366-1827C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD2	ENST00000322444.7 link	c.143C>T	p.Ala48Val	missense_variant	1/6	1	NM_015353.3	ENSP00000312814.6		Q14681

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

149148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000668

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000129

AC:

AN:

1004304

Hom.:

Cov.:

AF XY:

0.0000169

AC XY:

AN XY:

474188

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000211

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000574

Gnomad4 OTH exome

AF:

0.0000790

GnomAD4 genome

AF:

0.0000201

AC:

AN:

149256

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72822

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000667

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000481

Bravo

AF:

0.0000113

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

Jun 09, 2022

The c.143C>T (p.A48V) alteration is located in exon 1 (coding exon 1) of the KCTD2 gene. This alteration results from a C to T substitution at nucleotide position 143, causing the alanine (A) at amino acid position 48 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

0.089

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0046

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.50

M_CAP

Pathogenic

0.39

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.26

REVEL

Benign

0.10

Sift

Benign

0.16

Sift4G

Benign

0.068

Polyphen

0.0080

Vest4

0.089

MutPred

0.38

Gain of sheet (P = 0.0344);

MVP

0.41

MPC

1.0

ClinPred

0.15

GERP RS

3.5

Varity_R

0.079

gMVP

0.36

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