19-36086677-C-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.1643-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,594,750 control chromosomes in the GnomAD database, including 10,145 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: 31)

Exomes 𝑓: 0.10 ( 8421 hom. )

Consequence

WDR62
NM_001083961.2 intron

Scores

Splicing: ADA: 0.00001701

Clinical Significance

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

Conservation

PhyloP100: 0.314

Publications

6 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 (BayesDel_noAF=-0.81).

BP6

Variant 19-36086677-C-T is Benign according to our data. Variant chr19-36086677-C-T is described in ClinVar as Benign. ClinVar VariationId is 160253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR62	NM_001083961.2 link	c.1643-10C>T		intron_variant	Intron 12 of 31	ENST00000401500.7	NP_001077430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR62	ENST00000401500.7 link	c.1643-10C>T		intron_variant	Intron 12 of 31	1	NM_001083961.2	ENSP00000384792.1

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

20710

AN:

152056

Hom.:

1724

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.107

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0890

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.154

GnomAD2 exomes

AF:

0.100

AC:

22190

AN:

220914

AF XY:

0.101

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.0727

Gnomad ASJ exome

AF:

0.128

Gnomad EAS exome

AF:

0.000176

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.117

GnomAD4 exome

AF:

0.104

AC:

149311

AN:

1442576

Hom.:

8421

Cov.:

AF XY:

0.104

AC XY:

74292

AN XY:

715818

show subpopulations

African (AFR)

AF:

0.227

AC:

7507

AN:

32998

American (AMR)

AF:

0.0766

AC:

3261

AN:

42590

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

3129

AN:

25718

East Asian (EAS)

AF:

0.000436

AC:

AN:

38980

South Asian (SAS)

AF:

0.0916

AC:

7643

AN:

83458

European-Finnish (FIN)

AF:

0.109

AC:

5624

AN:

51802

Middle Eastern (MID)

AF:

0.194

AC:

1115

AN:

5752

European-Non Finnish (NFE)

AF:

0.104

AC:

114351

AN:

1101686

Other (OTH)

AF:

0.112

AC:

6664

AN:

59592

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

7470

14940

22410

29880

37350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4152

8304

12456

16608

20760

<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:

20723

AN:

152174

Hom.:

1724

Cov.:

AF XY:

0.135

AC XY:

10038

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.223

AC:

9262

AN:

41492

American (AMR)

AF:

0.107

AC:

1629

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

459

AN:

3470

East Asian (EAS)

AF:

0.000772

AC:

AN:

5182

South Asian (SAS)

AF:

0.0891

AC:

429

AN:

4816

European-Finnish (FIN)

AF:

0.116

AC:

1228

AN:

10604

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.106

AC:

7209

AN:

68006

Other (OTH)

AF:

0.153

AC:

323

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

889

1778

2666

3555

4444

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:

0.122

Hom.:

913

Bravo

AF:

0.141

Asia WGS

AF:

0.0520

AC:

182

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

- -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

Benign:3

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 09, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

not provided

Benign:3

Mar 03, 2015

GeneDx

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.0

(source)

DANN

Benign

0.58

PhyloP100

0.31

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000017

dbscSNV1_RF

Benign

0.0040

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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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