NM_001083961.2:c.3929A>T

Variant names:

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.3929A>T(p.Gln1310Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 1,610,952 control chromosomes in the GnomAD database, including 319,407 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 0.68 ( 35415 hom., cov: 33)

Exomes 𝑓: 0.62 ( 283992 hom. )

Consequence

WDR62
NM_001083961.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.510

Publications

32 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=1.1123858E-6).

BP6

Variant 19-36103757-A-T is Benign according to our data. Variant chr19-36103757-A-T is described in ClinVar as Benign. ClinVar VariationId is 93538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR62	NM_001083961.2 link	c.3929A>T	p.Gln1310Leu	missense_variant	Exon 30 of 32	ENST00000401500.7	NP_001077430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR62	ENST00000401500.7 link	c.3929A>T	p.Gln1310Leu	missense_variant	Exon 30 of 32	1	NM_001083961.2	ENSP00000384792.1

Frequencies

GnomAD3 genomes

AF:

0.676

AC:

102797

AN:

152006

Hom.:

35370

Cov.:

show subpopulations

Gnomad AFR

AF:

0.787

Gnomad AMI

AF:

0.393

Gnomad AMR

AF:

0.715

Gnomad ASJ

AF:

0.593

Gnomad EAS

AF:

0.786

Gnomad SAS

AF:

0.618

Gnomad FIN

AF:

0.654

Gnomad MID

AF:

0.661

Gnomad NFE

AF:

0.607

Gnomad OTH

AF:

0.675

GnomAD2 exomes

AF:

0.657

AC:

163767

AN:

249138

AF XY:

0.647

show subpopulations

Gnomad AFR exome

AF:

0.794

Gnomad AMR exome

AF:

0.761

Gnomad ASJ exome

AF:

0.598

Gnomad EAS exome

AF:

0.777

Gnomad FIN exome

AF:

0.643

Gnomad NFE exome

AF:

0.607

Gnomad OTH exome

AF:

0.635

GnomAD4 exome

AF:

0.622

AC:

906857

AN:

1458828

Hom.:

283992

Cov.:

AF XY:

0.621

AC XY:

450666

AN XY:

725884

show subpopulations

African (AFR)

AF:

0.795

AC:

26610

AN:

33478

American (AMR)

AF:

0.759

AC:

33920

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.588

AC:

15369

AN:

26134

East Asian (EAS)

AF:

0.800

AC:

31755

AN:

39696

South Asian (SAS)

AF:

0.613

AC:

52898

AN:

86252

European-Finnish (FIN)

AF:

0.641

AC:

32385

AN:

50538

Middle Eastern (MID)

AF:

0.585

AC:

3377

AN:

5768

European-Non Finnish (NFE)

AF:

0.605

AC:

672651

AN:

1111872

Other (OTH)

AF:

0.628

AC:

37892

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

24243

48486

72729

96972

121215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18400

36800

55200

73600

92000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.676

AC:

102900

AN:

152124

Hom.:

35415

Cov.:

AF XY:

0.679

AC XY:

50473

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.788

AC:

32691

AN:

41506

American (AMR)

AF:

0.715

AC:

10944

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.593

AC:

2056

AN:

3470

East Asian (EAS)

AF:

0.786

AC:

4058

AN:

5160

South Asian (SAS)

AF:

0.617

AC:

2981

AN:

4828

European-Finnish (FIN)

AF:

0.654

AC:

6929

AN:

10588

Middle Eastern (MID)

AF:

0.656

AC:

193

AN:

294

European-Non Finnish (NFE)

AF:

0.607

AC:

41263

AN:

67956

Other (OTH)

AF:

0.676

AC:

1427

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1719

3438

5157

6876

8595

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

808

1616

2424

3232

4040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.633

Hom.:

7257

Bravo

AF:

0.687

TwinsUK

AF:

0.604

AC:

2239

ALSPAC

AF:

0.602

AC:

2321

ESP6500AA

AF:

0.783

AC:

3451

ESP6500EA

AF:

0.605

AC:

5204

ExAC

AF:

0.653

AC:

79225

Asia WGS

AF:

0.727

AC:

2528

AN:

3478

EpiCase

AF:

0.614

EpiControl

AF:

0.608

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 12, 2013

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

- -

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 12, 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. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

- -

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

0.057

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.74

CADD

Benign

7.1

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.00077

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0034

LIST_S2

Benign

0.25

T;T

MetaRNN

Benign

0.0000011

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.5

.;N

PhyloP100

0.51

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.030

N;N

REVEL

Benign

0.026

Sift

Benign

0.19

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.0

B;B

Vest4

0.036

MPC

0.21

ClinPred

0.0057

GERP RS

2.1

Varity_R

0.053

gMVP

0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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