rs2074435

Positions:

chr19-36103757-A-T

Variant summary

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

The NM_001083961.2(WDR62):c.3929A>T(p.Gln1310Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 1,610,952 control chromosomes in the GnomAD database, including 319,407 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 ( 35415 hom., cov: 33)

Exomes 𝑓: 0.62 ( 283992 hom. )

Consequence

WDR62
NM_001083961.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.510

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=1.1123858E-6).

BP6

Variant 19-36103757-A-T is Benign according to our data. Variant chr19-36103757-A-T is described in ClinVar as [Benign]. Clinvar id is 93538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-36103757-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 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.3929A>T	p.Gln1310Leu	missense_variant	30/32	ENST00000401500.7	NP_001077430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR62	ENST00000401500.7 linkuse as main transcript	c.3929A>T	p.Gln1310Leu	missense_variant	30/32	1	NM_001083961.2	ENSP00000384792	P4	O43379-4

Frequencies

GnomAD3 genomes

AF:

0.676

AC:

102797

AN:

152006

Hom.:

35370

Cov.:

show subpopulations

Gnomad AFR

AF:

0.787

Gnomad AMI

AF:

0.393

Gnomad AMR

AF:

0.715

Gnomad ASJ

AF:

0.593

Gnomad EAS

AF:

0.786

Gnomad SAS

AF:

0.618

Gnomad FIN

AF:

0.654

Gnomad MID

AF:

0.661

Gnomad NFE

AF:

0.607

Gnomad OTH

AF:

0.675

GnomAD3 exomes

AF:

0.657

AC:

163767

AN:

249138

Hom.:

54611

AF XY:

0.647

AC XY:

87355

AN XY:

134952

show subpopulations

Gnomad AFR exome

AF:

0.794

Gnomad AMR exome

AF:

0.761

Gnomad ASJ exome

AF:

0.598

Gnomad EAS exome

AF:

0.777

Gnomad SAS exome

AF:

0.614

Gnomad FIN exome

AF:

0.643

Gnomad NFE exome

AF:

0.607

Gnomad OTH exome

AF:

0.635

GnomAD4 exome

AF:

0.622

AC:

906857

AN:

1458828

Hom.:

283992

Cov.:

AF XY:

0.621

AC XY:

450666

AN XY:

725884

show subpopulations

Gnomad4 AFR exome

AF:

0.795

Gnomad4 AMR exome

AF:

0.759

Gnomad4 ASJ exome

AF:

0.588

Gnomad4 EAS exome

AF:

0.800

Gnomad4 SAS exome

AF:

0.613

Gnomad4 FIN exome

AF:

0.641

Gnomad4 NFE exome

AF:

0.605

Gnomad4 OTH exome

AF:

0.628

GnomAD4 genome

AF:

0.676

AC:

102900

AN:

152124

Hom.:

35415

Cov.:

AF XY:

0.679

AC XY:

50473

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.788

Gnomad4 AMR

AF:

0.715

Gnomad4 ASJ

AF:

0.593

Gnomad4 EAS

AF:

0.786

Gnomad4 SAS

AF:

0.617

Gnomad4 FIN

AF:

0.654

Gnomad4 NFE

AF:

0.607

Gnomad4 OTH

AF:

0.676

Alfa

AF:

0.633

Hom.:

7257

Bravo

AF:

0.687

TwinsUK

AF:

0.604

AC:

2239

ALSPAC

AF:

0.602

AC:

2321

ESP6500AA

AF:

0.783

AC:

3451

ESP6500EA

AF:

0.605

AC:

5204

ExAC

AF:

0.653

AC:

79225

Asia WGS

AF:

0.727

AC:

2528

AN:

3478

EpiCase

AF:

0.614

EpiControl

AF:

0.608

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 12, 2013	- -
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	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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

Benign:4

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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	Genome-Nilou Lab	Dec 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
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	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.74

CADD

Benign

7.1

DANN

Benign

0.71

DEOGEN2

Benign

0.00077

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0034

LIST_S2

Benign

0.25

T;T

MetaRNN

Benign

0.0000011

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.5

.;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.030

N;N

REVEL

Benign

0.026

Sift

Benign

0.19

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.0

B;B

Vest4

0.036

MPC

0.21

ClinPred

0.0057

GERP RS

2.1

Varity_R

0.053

gMVP

0.13

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