Genetic Variant NM_001083961.2:c.3639C>T (chr19-36103467-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001083961.2(WDR62):c.3639C>T(p.Ser1213Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0372 in 1,614,136 control chromosomes in the GnomAD database, including 1,424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 126 hom., cov: 33)

Exomes 𝑓: 0.038 ( 1298 hom. )

Consequence

WDR62
NM_001083961.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.687

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 (BayesDel_noAF=-0.72).

BP6

Variant 19-36103467-C-T is Benign according to our data. Variant chr19-36103467-C-T is described in ClinVar as [Benign]. Clinvar id is 160294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-36103467-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR62	NM_001083961.2 link	c.3639C>T	p.Ser1213Ser	synonymous_variant	Exon 30 of 32	ENST00000401500.7	NP_001077430.1	O43379-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR62	ENST00000401500.7 link	c.3639C>T	p.Ser1213Ser	synonymous_variant	Exon 30 of 32	1	NM_001083961.2	ENSP00000384792.1		O43379-4

Frequencies

GnomAD3 genomes

AF:

0.0326

AC:

4967

AN:

152154

Hom.:

123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0144

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0269

Gnomad ASJ

AF:

0.0634

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.0640

Gnomad FIN

AF:

0.0308

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0357

Gnomad OTH

AF:

0.0387

GnomAD3 exomes

AF:

0.0435

AC:

10947

AN:

251382

Hom.:

311

AF XY:

0.0450

AC XY:

6114

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.0154

Gnomad AMR exome

AF:

0.0195

Gnomad ASJ exome

AF:

0.0633

Gnomad EAS exome

AF:

0.121

Gnomad SAS exome

AF:

0.0647

Gnomad FIN exome

AF:

0.0328

Gnomad NFE exome

AF:

0.0370

Gnomad OTH exome

AF:

0.0414

GnomAD4 exome

AF:

0.0377

AC:

55110

AN:

1461864

Hom.:

1298

Cov.:

AF XY:

0.0387

AC XY:

28116

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0140

Gnomad4 AMR exome

AF:

0.0203

Gnomad4 ASJ exome

AF:

0.0666

Gnomad4 EAS exome

AF:

0.104

Gnomad4 SAS exome

AF:

0.0612

Gnomad4 FIN exome

AF:

0.0328

Gnomad4 NFE exome

AF:

0.0341

Gnomad4 OTH exome

AF:

0.0452

GnomAD4 genome

AF:

0.0327

AC:

4974

AN:

152272

Hom.:

126

Cov.:

AF XY:

0.0328

AC XY:

2445

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0143

Gnomad4 AMR

AF:

0.0268

Gnomad4 ASJ

AF:

0.0634

Gnomad4 EAS

AF:

0.111

Gnomad4 SAS

AF:

0.0637

Gnomad4 FIN

AF:

0.0308

Gnomad4 NFE

AF:

0.0358

Gnomad4 OTH

AF:

0.0430

Alfa

AF:

0.0352

Hom.:

Bravo

AF:

0.0309

Asia WGS

AF:

0.132

AC:

458

AN:

3478

EpiCase

AF:

0.0378

EpiControl

AF:

0.0348

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

Benign:3

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jun 05, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

6.7

DANN

Benign

0.57

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