rs17851503

Positions:

chr19-36103951-G-A

Variant summary

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

The NM_001083961.2(WDR62):c.4123G>A(p.Gly1375Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0435 in 1,598,538 control chromosomes in the GnomAD database, including 1,760 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 0.035 ( 140 hom., cov: 33)

Exomes 𝑓: 0.044 ( 1620 hom. )

Consequence

WDR62
NM_001083961.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0300

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=0.0016288757).

BP6

Variant 19-36103951-G-A is Benign according to our data. Variant chr19-36103951-G-A is described in ClinVar as [Benign]. Clinvar id is 160298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-36103951-G-A is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0611 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.4123G>A	p.Gly1375Ser	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.4123G>A	p.Gly1375Ser	missense_variant	30/32	1	NM_001083961.2	ENSP00000384792	P4	O43379-4

Frequencies

GnomAD3 genomes

AF:

0.0351

AC:

5339

AN:

152184

Hom.:

140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00864

Gnomad AMI

AF:

0.0582

Gnomad AMR

AF:

0.0374

Gnomad ASJ

AF:

0.0625

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0215

Gnomad FIN

AF:

0.0486

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0497

Gnomad OTH

AF:

0.0492

GnomAD3 exomes

AF:

0.0380

AC:

9043

AN:

237866

Hom.:

234

AF XY:

0.0393

AC XY:

5092

AN XY:

129698

show subpopulations

Gnomad AFR exome

AF:

0.00738

Gnomad AMR exome

AF:

0.0291

Gnomad ASJ exome

AF:

0.0616

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.0228

Gnomad FIN exome

AF:

0.0481

Gnomad NFE exome

AF:

0.0517

Gnomad OTH exome

AF:

0.0470

GnomAD4 exome

AF:

0.0444

AC:

64192

AN:

1446236

Hom.:

1620

Cov.:

AF XY:

0.0443

AC XY:

31897

AN XY:

719846

show subpopulations

Gnomad4 AFR exome

AF:

0.00783

Gnomad4 AMR exome

AF:

0.0299

Gnomad4 ASJ exome

AF:

0.0559

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0224

Gnomad4 FIN exome

AF:

0.0459

Gnomad4 NFE exome

AF:

0.0490

Gnomad4 OTH exome

AF:

0.0438

GnomAD4 genome

AF:

0.0350

AC:

5338

AN:

152302

Hom.:

140

Cov.:

AF XY:

0.0349

AC XY:

2599

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00864

Gnomad4 AMR

AF:

0.0373

Gnomad4 ASJ

AF:

0.0625

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0216

Gnomad4 FIN

AF:

0.0486

Gnomad4 NFE

AF:

0.0497

Gnomad4 OTH

AF:

0.0487

Alfa

AF:

0.0493

Hom.:

100

Bravo

AF:

0.0345

TwinsUK

AF:

0.0461

AC:

171

ALSPAC

AF:

0.0488

AC:

188

ESP6500AA

AF:

0.00862

AC:

ESP6500EA

AF:

0.0453

AC:

390

ExAC

AF:

0.0381

AC:

4603

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0576

EpiControl

AF:

0.0601

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

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

Benign:3

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	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 05, 2017	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.054

DANN

Benign

0.36

DEOGEN2

Benign

0.0015

.;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.35

T;T

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.5

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

1.3

N;N

REVEL

Benign

0.017

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;B

Vest4

0.022

MPC

0.22

ClinPred

0.0000096

GERP RS

-1.6

Varity_R

0.033

gMVP

0.097

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