19-36099427-T-C

Position:

chr19-36099427-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001083961.2(WDR62):c.2549T>C(p.Leu850Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 1,613,118 control chromosomes in the GnomAD database, including 348,078 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 Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 35240 hom., cov: 32)

Exomes 𝑓: 0.65 ( 312838 hom. )

Consequence

WDR62
NM_001083961.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.558

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:

WDR62 (HGNC:):

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=1.7485688E-6).

BP6

Variant 19-36099427-T-C is Benign according to our data. Variant chr19-36099427-T-C is described in ClinVar as [Benign]. Clinvar id is 160269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-36099427-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR62	NM_001083961.2 linkuse as main transcript	c.2549T>C	p.Leu850Ser	missense_variant	22/32	ENST00000401500.7	NP_001077430.1	O43379-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR62	ENST00000401500.7 linkuse as main transcript	c.2549T>C	p.Leu850Ser	missense_variant	22/32	1	NM_001083961.2	ENSP00000384792.1		O43379-4

Frequencies

GnomAD3 genomes

AF:

0.678

AC:

103048

AN:

151954

Hom.:

35213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.729

Gnomad AMI

AF:

0.571

Gnomad AMR

AF:

0.682

Gnomad ASJ

AF:

0.603

Gnomad EAS

AF:

0.594

Gnomad SAS

AF:

0.509

Gnomad FIN

AF:

0.752

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.659

Gnomad OTH

AF:

0.677

GnomAD3 exomes

AF:

0.646

AC:

159945

AN:

247530

Hom.:

52234

AF XY:

0.638

AC XY:

85704

AN XY:

134434

show subpopulations

Gnomad AFR exome

AF:

0.729

Gnomad AMR exome

AF:

0.690

Gnomad ASJ exome

AF:

0.604

Gnomad EAS exome

AF:

0.583

Gnomad SAS exome

AF:

0.507

Gnomad FIN exome

AF:

0.737

Gnomad NFE exome

AF:

0.656

Gnomad OTH exome

AF:

0.638

GnomAD4 exome

AF:

0.653

AC:

953379

AN:

1461046

Hom.:

312838

Cov.:

AF XY:

0.649

AC XY:

471409

AN XY:

726864

show subpopulations

Gnomad4 AFR exome

AF:

0.734

Gnomad4 AMR exome

AF:

0.691

Gnomad4 ASJ exome

AF:

0.592

Gnomad4 EAS exome

AF:

0.613

Gnomad4 SAS exome

AF:

0.513

Gnomad4 FIN exome

AF:

0.734

Gnomad4 NFE exome

AF:

0.660

Gnomad4 OTH exome

AF:

0.638

GnomAD4 genome

AF:

0.678

AC:

103123

AN:

152072

Hom.:

35240

Cov.:

AF XY:

0.679

AC XY:

50483

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.728

Gnomad4 AMR

AF:

0.682

Gnomad4 ASJ

AF:

0.603

Gnomad4 EAS

AF:

0.594

Gnomad4 SAS

AF:

0.509

Gnomad4 FIN

AF:

0.752

Gnomad4 NFE

AF:

0.659

Gnomad4 OTH

AF:

0.674

Alfa

AF:

0.653

Hom.:

75525

Bravo

AF:

0.679

TwinsUK

AF:

0.659

AC:

2445

ALSPAC

AF:

0.659

AC:

2539

ESP6500AA

AF:

0.721

AC:

3175

ESP6500EA

AF:

0.649

AC:

5584

ExAC

AF:

0.640

AC:

77628

Asia WGS

AF:

0.520

AC:

1811

AN:

3478

EpiCase

AF:

0.656

EpiControl

AF:

0.648

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 05, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.5

DANN

Benign

0.23

DEOGEN2

Benign

0.00085

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0033

LIST_S2

Benign

0.090

T;T

MetaRNN

Benign

0.0000017

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.1

N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

2.2

N;N

REVEL

Benign

0.10

Sift

Benign

1.0

T;T

Sift4G

Benign

0.91

T;T

Polyphen

0.0

B;B

Vest4

0.042

MPC

0.30

ClinPred

0.0056

GERP RS

4.3

Varity_R

0.025

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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