NM_001083961.2:c.142C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001083961.2(WDR62):c.142C>T(p.Leu48Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 1,607,278 control chromosomes in the GnomAD database, including 153 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 6 hom., cov: 33)

Exomes 𝑓: 0.014 ( 147 hom. )

Consequence

WDR62
NM_001083961.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 0.382

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042237043).

BP6

Variant 19-36055113-C-T is Benign according to our data. Variant chr19-36055113-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 93535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-36055113-C-T is described in Lovd as [Benign]. Variant chr19-36055113-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00772 (1176/152240) while in subpopulation NFE AF= 0.0137 (932/67994). AF 95% confidence interval is 0.013. There are 6 homozygotes in gnomad4. There are 520 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR62	NM_001083961.2 link	c.142C>T	p.Leu48Phe	missense_variant	Exon 1 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.142C>T	p.Leu48Phe	missense_variant	Exon 1 of 32	1	NM_001083961.2	ENSP00000384792.1		O43379-4

Frequencies

GnomAD3 genomes

AF:

0.00773

AC:

1176

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00307

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0137

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00715

AC:

1638

AN:

229006

Hom.:

AF XY:

0.00735

AC XY:

930

AN XY:

126458

show subpopulations

Gnomad AFR exome

AF:

0.00274

Gnomad AMR exome

AF:

0.00205

Gnomad ASJ exome

AF:

0.00156

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00405

Gnomad FIN exome

AF:

0.00232

Gnomad NFE exome

AF:

0.0130

Gnomad OTH exome

AF:

0.00657

GnomAD4 exome

AF:

0.0135

AC:

19664

AN:

1455038

Hom.:

147

Cov.:

AF XY:

0.0132

AC XY:

9542

AN XY:

723542

show subpopulations

Gnomad4 AFR exome

AF:

0.00201

Gnomad4 AMR exome

AF:

0.00232

Gnomad4 ASJ exome

AF:

0.00212

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00409

Gnomad4 FIN exome

AF:

0.00267

Gnomad4 NFE exome

AF:

0.0166

Gnomad4 OTH exome

AF:

0.00936

GnomAD4 genome

AF:

0.00772

AC:

1176

AN:

152240

Hom.:

Cov.:

AF XY:

0.00699

AC XY:

520

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00306

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00264

Gnomad4 NFE

AF:

0.0137

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.0122

Hom.:

Bravo

AF:

0.00789

TwinsUK

AF:

0.0119

AC:

ALSPAC

AF:

0.0166

AC:

ESP6500AA

AF:

0.00326

AC:

ESP6500EA

AF:

0.0104

AC:

ExAC

AF:

0.00645

AC:

770

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

WDR62: BP4, BS1, BS2 -

Jan 11, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:4

Aug 09, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 07, 2024

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

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

- -

Jun 23, 2016

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. -

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

Benign:4

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. -

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 21, 2015

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

Significance: Likely 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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0068

.;T;.

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.54

T;T;T

MetaRNN

Benign

0.0042

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.9

L;L;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.34

T;T;T

Sift4G

Benign

0.72

T;T;T

Polyphen

0.0030

B;B;.

Vest4

0.17

MVP

0.61

MPC

0.24

ClinPred

0.0078

GERP RS

4.3

Varity_R

0.076

gMVP

0.29

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over