19-36073544-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.1233+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0427 in 1,461,698 control chromosomes in the GnomAD database, including 1,604 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 145 hom., cov: 31)

Exomes 𝑓: 0.043 ( 1459 hom. )

Consequence

WDR62
NM_001083961.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.55

Publications

4 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=-0.82).

BP6

Variant 19-36073544-C-T is Benign according to our data. Variant chr19-36073544-C-T is described in ClinVar as Benign. ClinVar VariationId is 160245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR62	NM_001083961.2 link	c.1233+13C>T		intron_variant	Intron 9 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.1233+13C>T		intron_variant	Intron 9 of 31	1	NM_001083961.2	ENSP00000384792.1

Frequencies

GnomAD3 genomes

AF:

0.0358

AC:

5369

AN:

149890

Hom.:

142

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0218

Gnomad AMI

AF:

0.00887

Gnomad AMR

AF:

0.0286

Gnomad ASJ

AF:

0.0649

Gnomad EAS

AF:

0.112

Gnomad SAS

AF:

0.0810

Gnomad FIN

AF:

0.0318

Gnomad MID

AF:

0.0417

Gnomad NFE

AF:

0.0364

Gnomad OTH

AF:

0.0414

GnomAD2 exomes

AF:

0.0489

AC:

11518

AN:

235362

AF XY:

0.0503

show subpopulations

Gnomad AFR exome

AF:

0.0265

Gnomad AMR exome

AF:

0.0209

Gnomad ASJ exome

AF:

0.0673

Gnomad EAS exome

AF:

0.125

Gnomad FIN exome

AF:

0.0341

Gnomad NFE exome

AF:

0.0398

Gnomad OTH exome

AF:

0.0485

GnomAD4 exome

AF:

0.0435

AC:

56995

AN:

1311696

Hom.:

1459

Cov.:

AF XY:

0.0447

AC XY:

29326

AN XY:

656216

show subpopulations

African (AFR)

AF:

0.0232

AC:

708

AN:

30532

American (AMR)

AF:

0.0225

AC:

968

AN:

43034

Ashkenazi Jewish (ASJ)

AF:

0.0732

AC:

1776

AN:

24270

East Asian (EAS)

AF:

0.113

AC:

4134

AN:

36536

South Asian (SAS)

AF:

0.0784

AC:

6520

AN:

83182

European-Finnish (FIN)

AF:

0.0370

AC:

1721

AN:

46548

Middle Eastern (MID)

AF:

0.0490

AC:

264

AN:

5392

European-Non Finnish (NFE)

AF:

0.0385

AC:

38001

AN:

987626

Other (OTH)

AF:

0.0532

AC:

2903

AN:

54576

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.578

Heterozygous variant carriers

2770

5540

8311

11081

13851

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1502

3004

4506

6008

7510

<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:

0.0359

AC:

5380

AN:

150002

Hom.:

145

Cov.:

AF XY:

0.0362

AC XY:

2649

AN XY:

73222

show subpopulations

African (AFR)

AF:

0.0218

AC:

896

AN:

41120

American (AMR)

AF:

0.0286

AC:

433

AN:

15152

Ashkenazi Jewish (ASJ)

AF:

0.0649

AC:

222

AN:

3420

East Asian (EAS)

AF:

0.112

AC:

566

AN:

5044

South Asian (SAS)

AF:

0.0807

AC:

380

AN:

4708

European-Finnish (FIN)

AF:

0.0318

AC:

324

AN:

10194

Middle Eastern (MID)

AF:

0.0448

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0364

AC:

2443

AN:

67098

Other (OTH)

AF:

0.0458

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.584

Heterozygous variant carriers

215

430

646

861

1076

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0248

Hom.:

Bravo

AF:

0.0338

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

- -

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:2

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:2

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.28

(source)

DANN

Benign

0.69

PhyloP100

-1.6

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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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