19-36103013-T-G

Position:

chr19-36103013-T-G

Variant summary

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

The NM_001083961.2(WDR62):c.3401T>G(p.Met1134Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0386 in 1,614,088 control chromosomes in the GnomAD database, including 1,543 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 0.036 ( 140 hom., cov: 33)

Exomes 𝑓: 0.039 ( 1403 hom. )

Consequence

WDR62
NM_001083961.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.51

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=0.0021208823).

BP6

Variant 19-36103013-T-G is Benign according to our data. Variant chr19-36103013-T-G is described in ClinVar as [Benign]. Clinvar id is 160285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-36103013-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.104 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.3401T>G	p.Met1134Arg	missense_variant	28/32	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.3401T>G	p.Met1134Arg	missense_variant	28/32	1	NM_001083961.2	ENSP00000384792.1		O43379-4

Frequencies

GnomAD3 genomes

AF:

0.0356

AC:

5423

AN:

152180

Hom.:

137

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0221

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0287

Gnomad ASJ

AF:

0.0642

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.0786

Gnomad FIN

AF:

0.0309

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0360

Gnomad OTH

AF:

0.0425

GnomAD3 exomes

AF:

0.0459

AC:

11535

AN:

251038

Hom.:

346

AF XY:

0.0478

AC XY:

6490

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.0228

Gnomad AMR exome

AF:

0.0206

Gnomad ASJ exome

AF:

0.0652

Gnomad EAS exome

AF:

0.122

Gnomad SAS exome

AF:

0.0769

Gnomad FIN exome

AF:

0.0329

Gnomad NFE exome

AF:

0.0372

Gnomad OTH exome

AF:

0.0447

GnomAD4 exome

AF:

0.0389

AC:

56848

AN:

1461790

Hom.:

1403

Cov.:

AF XY:

0.0402

AC XY:

29223

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.0210

Gnomad4 AMR exome

AF:

0.0216

Gnomad4 ASJ exome

AF:

0.0681

Gnomad4 EAS exome

AF:

0.104

Gnomad4 SAS exome

AF:

0.0729

Gnomad4 FIN exome

AF:

0.0328

Gnomad4 NFE exome

AF:

0.0342

Gnomad4 OTH exome

AF:

0.0478

GnomAD4 genome

AF:

0.0357

AC:

5434

AN:

152298

Hom.:

140

Cov.:

AF XY:

0.0361

AC XY:

2686

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0221

Gnomad4 AMR

AF:

0.0287

Gnomad4 ASJ

AF:

0.0642

Gnomad4 EAS

AF:

0.112

Gnomad4 SAS

AF:

0.0783

Gnomad4 FIN

AF:

0.0309

Gnomad4 NFE

AF:

0.0360

Gnomad4 OTH

AF:

0.0468

Alfa

AF:

0.0365

Hom.:

Bravo

AF:

0.0337

TwinsUK

AF:

0.0337

AC:

125

ALSPAC

AF:

0.0327

AC:

126

ESP6500AA

AF:

0.0254

AC:

112

ESP6500EA

AF:

0.0392

AC:

337

ExAC

AF:

0.0474

AC:

5758

Asia WGS

AF:

0.151

AC:

523

AN:

3478

EpiCase

AF:

0.0380

EpiControl

AF:

0.0351

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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

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	Athena Diagnostics	Jun 05, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.21

DANN

Benign

0.28

DEOGEN2

Benign

0.0075

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.25

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

.;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.65

N;N

REVEL

Benign

0.022

Sift

Benign

0.053

T;T

Sift4G

Benign

0.59

T;T

Polyphen

0.024

B;B

Vest4

0.096

MPC

0.35

ClinPred

0.0022

GERP RS

-5.3

Varity_R

0.30

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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