19-36103161-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001083961.2(WDR62):c.3468C>T(p.Leu1156Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,613,930 control chromosomes in the GnomAD database, including 10,318 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1724 hom., cov: 33)

Exomes 𝑓: 0.10 ( 8594 hom. )

Consequence

WDR62
NM_001083961.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.94

Publications

9 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 19-36103161-C-T is Benign according to our data. Variant chr19-36103161-C-T is described in ClinVar as Benign. ClinVar VariationId is 160287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.94 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR62	NM_001083961.2 link	c.3468C>T	p.Leu1156Leu	synonymous_variant	Exon 29 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.3468C>T	p.Leu1156Leu	synonymous_variant	Exon 29 of 32	1	NM_001083961.2	ENSP00000384792.1		O43379-4

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

20728

AN:

152070

Hom.:

1724

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.119

Gnomad AMR

AF:

0.107

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.0893

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.155

GnomAD2 exomes

AF:

0.104

AC:

26021

AN:

250954

AF XY:

0.104

show subpopulations

Gnomad AFR exome

AF:

0.227

Gnomad AMR exome

AF:

0.0733

Gnomad ASJ exome

AF:

0.129

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.111

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.104

AC:

151692

AN:

1461742

Hom.:

8594

Cov.:

AF XY:

0.104

AC XY:

75685

AN XY:

727176

show subpopulations

African (AFR)

AF:

0.227

AC:

7616

AN:

33480

American (AMR)

AF:

0.0771

AC:

3446

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.123

AC:

3205

AN:

26136

East Asian (EAS)

AF:

0.000428

AC:

AN:

39698

South Asian (SAS)

AF:

0.0912

AC:

7863

AN:

86254

European-Finnish (FIN)

AF:

0.109

AC:

5822

AN:

53290

Middle Eastern (MID)

AF:

0.193

AC:

1114

AN:

5768

European-Non Finnish (NFE)

AF:

0.104

AC:

115846

AN:

1112004

Other (OTH)

AF:

0.112

AC:

6763

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

9973

19946

29919

39892

49865

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4166

8332

12498

16664

20830

<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:

0.136

AC:

20741

AN:

152188

Hom.:

1724

Cov.:

AF XY:

0.135

AC XY:

10052

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.224

AC:

9281

AN:

41516

American (AMR)

AF:

0.106

AC:

1627

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

456

AN:

3470

East Asian (EAS)

AF:

0.000773

AC:

AN:

5172

South Asian (SAS)

AF:

0.0893

AC:

431

AN:

4824

European-Finnish (FIN)

AF:

0.116

AC:

1227

AN:

10606

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.106

AC:

7211

AN:

67982

Other (OTH)

AF:

0.153

AC:

323

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

887

1774

2661

3548

4435

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

220

440

660

880

1100

<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:

0.118

Hom.:

2112

Bravo

AF:

0.141

Asia WGS

AF:

0.0510

AC:

180

AN:

3478

EpiCase

AF:

0.123

EpiControl

AF:

0.130

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

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

- -

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:3

Jun 05, 2017

Athena Diagnostics

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

- -

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:3

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

2.1

(source)

DANN

Benign

0.42

PhyloP100

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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