rs1008328

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001083961.2(WDR62):c.4170A>C(p.Leu1390Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 1,613,644 control chromosomes in the GnomAD database, including 469,035 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 Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 42774 hom., cov: 32)

Exomes 𝑓: 0.76 ( 426261 hom. )

Consequence

WDR62
NM_001083961.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.126

Publications

36 publications found

Variant links:

Genes affected

WDR62 (HGNC:24502): (WD repeat domain 62) This gene is proposed to play a role in cerebral cortical development. Mutations in this gene have been associated with microencephaly, cortical malformations, and cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2011]

WDR62 Gene-Disease associations (from GenCC):

microcephaly 2, primary, autosomal recessive, with or without cortical malformations
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, Illumina, G2P, ClinGen
autosomal recessive primary microcephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

WDR62 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.692469E-7).

BP6

Variant 19-36104534-A-C is Benign according to our data. Variant chr19-36104534-A-C is described in ClinVar as [Benign]. Clinvar id is 160301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR62	NM_001083961.2 link	c.4170A>C	p.Leu1390Phe	missense_variant	Exon 31 of 32	ENST00000401500.7	NP_001077430.1	O43379-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR62	ENST00000401500.7 link	c.4170A>C	p.Leu1390Phe	missense_variant	Exon 31 of 32	1	NM_001083961.2	ENSP00000384792.1		O43379-4

Frequencies

GnomAD3 genomes

AF:

0.749

AC:

113841

AN:

151982

Hom.:

42761

Cov.:

show subpopulations

Gnomad AFR

AF:

0.700

Gnomad AMI

AF:

0.616

Gnomad AMR

AF:

0.786

Gnomad ASJ

AF:

0.759

Gnomad EAS

AF:

0.747

Gnomad SAS

AF:

0.599

Gnomad FIN

AF:

0.782

Gnomad MID

AF:

0.782

Gnomad NFE

AF:

0.777

Gnomad OTH

AF:

0.759

GnomAD2 exomes

AF:

0.750

AC:

188442

AN:

251128

AF XY:

0.745

show subpopulations

Gnomad AFR exome

AF:

0.698

Gnomad AMR exome

AF:

0.807

Gnomad ASJ exome

AF:

0.760

Gnomad EAS exome

AF:

0.750

Gnomad FIN exome

AF:

0.770

Gnomad NFE exome

AF:

0.774

Gnomad OTH exome

AF:

0.764

GnomAD4 exome

AF:

0.762

AC:

1114342

AN:

1461544

Hom.:

426261

Cov.:

AF XY:

0.759

AC XY:

551863

AN XY:

727086

show subpopulations

African (AFR)

AF:

0.700

AC:

23442

AN:

33480

American (AMR)

AF:

0.806

AC:

36060

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.752

AC:

19654

AN:

26128

East Asian (EAS)

AF:

0.769

AC:

30525

AN:

39700

South Asian (SAS)

AF:

0.617

AC:

53253

AN:

86254

European-Finnish (FIN)

AF:

0.775

AC:

41177

AN:

53152

Middle Eastern (MID)

AF:

0.757

AC:

4366

AN:

5768

European-Non Finnish (NFE)

AF:

0.774

AC:

860623

AN:

1111958

Other (OTH)

AF:

0.749

AC:

45242

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

17423

34846

52268

69691

87114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.749

AC:

113895

AN:

152100

Hom.:

42774

Cov.:

AF XY:

0.748

AC XY:

55623

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.699

AC:

28992

AN:

41464

American (AMR)

AF:

0.786

AC:

12017

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.759

AC:

2634

AN:

3470

East Asian (EAS)

AF:

0.746

AC:

3844

AN:

5152

South Asian (SAS)

AF:

0.599

AC:

2889

AN:

4822

European-Finnish (FIN)

AF:

0.782

AC:

8286

AN:

10594

Middle Eastern (MID)

AF:

0.786

AC:

231

AN:

294

European-Non Finnish (NFE)

AF:

0.777

AC:

52842

AN:

67994

Other (OTH)

AF:

0.757

AC:

1601

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1488

2975

4463

5950

7438

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.768

Hom.:

117215

Bravo

AF:

0.751

TwinsUK

AF:

0.770

AC:

2854

ALSPAC

AF:

0.769

AC:

2965

ESP6500AA

AF:

0.696

AC:

3066

ESP6500EA

AF:

0.776

AC:

6676

ExAC

AF:

0.742

AC:

90139

Asia WGS

AF:

0.636

AC:

2212

AN:

3478

EpiCase

AF:

0.782

EpiControl

AF:

0.785

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Jan 24, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Microcephaly 2, primary, autosomal recessive, with or without cortical malformations

Benign:4

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:4

Jun 05, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.3

(source)

DANN

Benign

0.54

DEOGEN2

Benign

0.00089

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0017

LIST_S2

Benign

0.083

T;T

MetaRNN

Benign

9.7e-7

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.34

.;N

PhyloP100

-0.13

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.38

N;N

REVEL

Benign

0.055

Sift

Benign

0.31

T;T

Sift4G

Benign

0.56

T;T

Polyphen

0.0020

B;B

Vest4

0.029

MutPred

0.36

.;Loss of phosphorylation at S1388 (P = 0.1262);

MPC

0.24

ClinPred

0.0034

GERP RS

2.0

Varity_R

0.047

gMVP

0.045

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs1008328

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over