Variant 3-49012870-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_018031.6(WDR6):c.1336C>T(p.Arg446Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000954 in 1,613,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

WDR6
NM_018031.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.00

Variant links:

Genes affected

WDR6 (HGNC:12758): (WD repeat domain 6) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. The encoded protein interacts with serine/threonine kinase 11, and is implicated in cell growth arrest. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2016]

WDR6 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=0.23523974).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
WDR6	NM_018031.6 linkuse as main transcript	c.1336C>T	p.Arg446Cys	missense_variant	2/6	ENST00000608424.6
WDR6	NM_001320546.3 linkuse as main transcript	c.1258C>T	p.Arg420Cys	missense_variant	2/6
WDR6	NM_001320547.2 linkuse as main transcript	c.1183C>T	p.Arg395Cys	missense_variant	2/6
WDR6	XM_047447371.1 linkuse as main transcript	c.1336C>T	p.Arg446Cys	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR6	ENST00000608424.6 linkuse as main transcript	c.1336C>T	p.Arg446Cys	missense_variant	2/6	1	NM_018031.6	P2

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

151926

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.0000946

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.0000758

AC:

AN:

250570

Hom.:

AF XY:

0.0000664

AC XY:

AN XY:

135500

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000233

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000985

AC:

144

AN:

1461518

Hom.:

Cov.:

AF XY:

0.0000784

AC XY:

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000118

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000658

AC:

AN:

151926

Hom.:

Cov.:

AF XY:

0.0000943

AC XY:

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000946

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.0000386

Hom.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Mar 23, 2023

The c.1426C>T (p.R476C) alteration is located in exon 2 (coding exon 2) of the WDR6 gene. This alteration results from a C to T substitution at nucleotide position 1426, causing the arginine (R) at amino acid position 476 to be replaced by a cysteine (C). 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

0.22

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Benign

-0.10

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.028

T;T;T;T

Eigen

Benign

0.14

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.53

M_CAP

Benign

0.019

MetaRNN

Benign

0.24

T;T;T;T

MetaSVM

Benign

-0.87

MutationTaster

Benign

0.96

D;N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.3

N;.;.;N

REVEL

Uncertain

0.32

Sift

Uncertain

0.015

D;.;.;D

Sift4G

Uncertain

0.014

D;D;D;D

Polyphen

1.0

.;.;D;D

Vest4

0.64

MVP

0.56

MPC

0.28

ClinPred

0.17

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.095

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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