rs12327568

Positions:

chr19-36067994-A-G

Variant summary

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

The NM_001083961.2(WDR62):c.866A>G(p.Lys289Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000851 in 1,613,976 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00047 ( 5 hom. )

Consequence

WDR62
NM_001083961.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.10

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=0.008493841).

BP6

Variant 19-36067994-A-G is Benign according to our data. Variant chr19-36067994-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 160308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-36067994-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00453 (690/152332) while in subpopulation AFR AF= 0.0161 (668/41580). AF 95% confidence interval is 0.0151. There are 6 homozygotes in gnomad4. There are 321 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR62	NM_001083961.2 linkuse as main transcript	c.866A>G	p.Lys289Arg	missense_variant	7/32	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.866A>G	p.Lys289Arg	missense_variant	7/32	1	NM_001083961.2	ENSP00000384792.1		O43379-4

Frequencies

GnomAD3 genomes

AF:

0.00453

AC:

689

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0161

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00115

AC:

288

AN:

250662

Hom.:

AF XY:

0.000878

AC XY:

119

AN XY:

135540

show subpopulations

Gnomad AFR exome

AF:

0.0163

Gnomad AMR exome

AF:

0.000522

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000467

AC:

683

AN:

1461644

Hom.:

Cov.:

AF XY:

0.000428

AC XY:

311

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.0169

Gnomad4 AMR exome

AF:

0.000627

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.000911

GnomAD4 genome

AF:

0.00453

AC:

690

AN:

152332

Hom.:

Cov.:

AF XY:

0.00431

AC XY:

321

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0161

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00139

Hom.:

Bravo

AF:

0.00509

ESP6500AA

AF:

0.0129

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00152

AC:

185

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 29, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Dec 08, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jul 13, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 13, 2024	- -

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

Benign:2

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	Genome-Nilou Lab	Dec 05, 2021	- -

not specified

Benign:1

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

0.12

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

.;T;.

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.80

T;T;T

MetaRNN

Benign

0.0085

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.9

L;L;.

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Benign

0.073

Sift

Benign

0.082

T;T;D

Sift4G

Uncertain

0.046

D;D;T

Polyphen

0.95

P;P;.

Vest4

0.44

MVP

0.49

MPC

0.61

ClinPred

0.053

GERP RS

4.7

Varity_R

0.14

gMVP

0.51

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