Variant chr21-42850065-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_018669.6(WDR4):c.1223C>T(p.Ala408Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000198 in 1,613,744 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 2 hom. )

Consequence

WDR4
NM_018669.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.786

Variant links:

Genes affected

WDR4 (HGNC:12756): (WD repeat domain 4) 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. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene is excluded as a candidate for a form of nonsyndromic deafness (DFNB10), but is still a candidate for other disorders mapped to 21q22.3 as well as for the development of Down syndrome phenotypes. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, May 2012]

WDR4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040081143).

BP6

Variant 21-42850065-G-A is Benign according to our data. Variant chr21-42850065-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2075990.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR4	NM_018669.6 linkuse as main transcript	c.1223C>T	p.Ala408Val	missense_variant	11/11	ENST00000398208.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR4	ENST00000398208.3 linkuse as main transcript	c.1223C>T	p.Ala408Val	missense_variant	11/11	1	NM_018669.6	P1	P57081-1
WDR4	ENST00000330317.6 linkuse as main transcript	c.1223C>T	p.Ala408Val	missense_variant	11/12	1		P1	P57081-1
WDR4	ENST00000476326.5 linkuse as main transcript	n.1138C>T		non_coding_transcript_exon_variant	11/11	1
WDR4	ENST00000492742.5 linkuse as main transcript	n.1366C>T		non_coding_transcript_exon_variant	11/11	2

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00405

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000383

AC:

AN:

250840

Hom.:

AF XY:

0.000369

AC XY:

AN XY:

135596

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00343

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000185

AC:

271

AN:

1461386

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

130

AN XY:

727020

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000449

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00313

Gnomad4 NFE exome

AF:

0.0000675

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000322

AC:

AN:

152358

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00405

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000567

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.000272

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 02, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.42

CADD

Benign

9.5

DANN

Benign

0.97

DEOGEN2

Benign

0.019

T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.40

.;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.0040

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.88

N;N

REVEL

Benign

0.072

Sift

Benign

0.13

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.81

P;P

Vest4

0.090

MVP

0.35

MPC

0.022

ClinPred

0.013

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.049

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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