19-36099427-T-C

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.2549T>C(p.Leu850Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 1,613,118 control chromosomes in the GnomAD database, including 348,078 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 ( 35240 hom., cov: 32)

Exomes 𝑓: 0.65 ( 312838 hom. )

Consequence

WDR62
NM_001083961.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.558

Publications

40 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=1.7485688E-6).

BP6

Variant 19-36099427-T-C is Benign according to our data. Variant chr19-36099427-T-C is described in ClinVar as Benign. ClinVar VariationId is 160269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR62	NM_001083961.2 link	c.2549T>C	p.Leu850Ser	missense_variant	Exon 22 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.2549T>C	p.Leu850Ser	missense_variant	Exon 22 of 32	1	NM_001083961.2	ENSP00000384792.1

Frequencies

GnomAD3 genomes

AF:

0.678

AC:

103048

AN:

151954

Hom.:

35213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.729

Gnomad AMI

AF:

0.571

Gnomad AMR

AF:

0.682

Gnomad ASJ

AF:

0.603

Gnomad EAS

AF:

0.594

Gnomad SAS

AF:

0.509

Gnomad FIN

AF:

0.752

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.659

Gnomad OTH

AF:

0.677

GnomAD2 exomes

AF:

0.646

AC:

159945

AN:

247530

AF XY:

0.638

show subpopulations

Gnomad AFR exome

AF:

0.729

Gnomad AMR exome

AF:

0.690

Gnomad ASJ exome

AF:

0.604

Gnomad EAS exome

AF:

0.583

Gnomad FIN exome

AF:

0.737

Gnomad NFE exome

AF:

0.656

Gnomad OTH exome

AF:

0.638

GnomAD4 exome

AF:

0.653

AC:

953379

AN:

1461046

Hom.:

312838

Cov.:

AF XY:

0.649

AC XY:

471409

AN XY:

726864

show subpopulations

African (AFR)

AF:

0.734

AC:

24577

AN:

33476

American (AMR)

AF:

0.691

AC:

30900

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.592

AC:

15462

AN:

26120

East Asian (EAS)

AF:

0.613

AC:

24326

AN:

39700

South Asian (SAS)

AF:

0.513

AC:

44212

AN:

86254

European-Finnish (FIN)

AF:

0.734

AC:

38785

AN:

52826

Middle Eastern (MID)

AF:

0.578

AC:

3307

AN:

5724

European-Non Finnish (NFE)

AF:

0.660

AC:

733310

AN:

1111894

Other (OTH)

AF:

0.638

AC:

38500

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

20010

40020

60031

80041

100051

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19144

38288

57432

76576

95720

<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:

0.678

AC:

103123

AN:

152072

Hom.:

35240

Cov.:

AF XY:

0.679

AC XY:

50483

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.728

AC:

30231

AN:

41500

American (AMR)

AF:

0.682

AC:

10428

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.603

AC:

2092

AN:

3468

East Asian (EAS)

AF:

0.594

AC:

3060

AN:

5150

South Asian (SAS)

AF:

0.509

AC:

2457

AN:

4824

European-Finnish (FIN)

AF:

0.752

AC:

7960

AN:

10582

Middle Eastern (MID)

AF:

0.633

AC:

186

AN:

294

European-Non Finnish (NFE)

AF:

0.659

AC:

44767

AN:

67948

Other (OTH)

AF:

0.674

AC:

1422

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1743

3486

5229

6972

8715

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

810

1620

2430

3240

4050

<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:

0.657

Hom.:

142810

Bravo

AF:

0.679

TwinsUK

AF:

0.659

AC:

2445

ALSPAC

AF:

0.659

AC:

2539

ESP6500AA

AF:

0.721

AC:

3175

ESP6500EA

AF:

0.649

AC:

5584

ExAC

AF:

0.640

AC:

77628

Asia WGS

AF:

0.520

AC:

1811

AN:

3478

EpiCase

AF:

0.656

EpiControl

AF:

0.648

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Benign:4

Dec 05, 2021

Genome-Nilou Lab

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

- -

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

- -

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. -

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

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

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

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

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

0.051

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.5

(source)

DANN

Benign

0.23

DEOGEN2

Benign

0.00085

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0033

LIST_S2

Benign

0.090

T;T

MetaRNN

Benign

0.0000017

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.1

N;N

PhyloP100

0.56

PrimateAI

Benign

0.40

PROVEAN

Benign

2.2

N;N

REVEL

Benign

0.10

Sift

Benign

1.0

T;T

Sift4G

Benign

0.91

T;T

Polyphen

0.0

B;B

Vest4

0.042

MPC

0.30

ClinPred

0.0056

GERP RS

4.3

Varity_R

0.025

gMVP

0.56

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