NM_001083961.2:c.186C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001083961.2(WDR62):c.186C>T(p.Leu62Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,612,986 control chromosomes in the GnomAD database, including 30,791 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L62L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.15 ( 2186 hom., cov: 33)

Exomes 𝑓: 0.19 ( 28605 hom. )

Consequence

WDR62
NM_001083961.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.79

Publications

14 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 19-36058788-C-T is Benign according to our data. Variant chr19-36058788-C-T is described in ClinVar as [Benign]. Clinvar id is 137909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.79 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR62	NM_001083961.2 link	c.186C>T	p.Leu62Leu	synonymous_variant	Exon 2 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.186C>T	p.Leu62Leu	synonymous_variant	Exon 2 of 32	1	NM_001083961.2	ENSP00000384792.1		O43379-4

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22924

AN:

152118

Hom.:

2185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0384

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.157

Gnomad ASJ

AF:

0.229

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.156

GnomAD2 exomes

AF:

0.179

AC:

44920

AN:

250836

AF XY:

0.184

show subpopulations

Gnomad AFR exome

AF:

0.0352

Gnomad AMR exome

AF:

0.150

Gnomad ASJ exome

AF:

0.223

Gnomad EAS exome

AF:

0.194

Gnomad FIN exome

AF:

0.166

Gnomad NFE exome

AF:

0.204

Gnomad OTH exome

AF:

0.198

GnomAD4 exome

AF:

0.195

AC:

284574

AN:

1460750

Hom.:

28605

Cov.:

AF XY:

0.195

AC XY:

141879

AN XY:

726702

show subpopulations

African (AFR)

AF:

0.0321

AC:

1074

AN:

33474

American (AMR)

AF:

0.150

AC:

6686

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

5986

AN:

26118

East Asian (EAS)

AF:

0.178

AC:

7059

AN:

39686

South Asian (SAS)

AF:

0.181

AC:

15585

AN:

86230

European-Finnish (FIN)

AF:

0.171

AC:

9145

AN:

53378

Middle Eastern (MID)

AF:

0.231

AC:

1326

AN:

5750

European-Non Finnish (NFE)

AF:

0.203

AC:

226097

AN:

1111078

Other (OTH)

AF:

0.193

AC:

11616

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

11867

23735

35602

47470

59337

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.151

AC:

22922

AN:

152236

Hom.:

2186

Cov.:

AF XY:

0.150

AC XY:

11140

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0383

AC:

1593

AN:

41574

American (AMR)

AF:

0.157

AC:

2402

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

796

AN:

3470

East Asian (EAS)

AF:

0.183

AC:

946

AN:

5168

South Asian (SAS)

AF:

0.169

AC:

815

AN:

4820

European-Finnish (FIN)

AF:

0.161

AC:

1705

AN:

10594

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.207

AC:

14068

AN:

67998

Other (OTH)

AF:

0.157

AC:

332

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1001

2001

3002

4002

5003

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.174

Hom.:

1649

Bravo

AF:

0.145

Asia WGS

AF:

0.162

AC:

564

AN:

3478

EpiCase

AF:

0.205

EpiControl

AF:

0.212

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Dec 17, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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

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:2

Feb 03, 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

-0.35

CADD

Benign

2.8

(source)

DANN

Benign

0.81

PhyloP100

-3.8

Mutation Taster

=92/8

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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NM_001083961.2:c.186C>T

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