Genetic Variant NM_001083961.2:c.180G>A (chr19-36058782-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001083961.2(WDR62):c.180G>A(p.Val60Val) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0519 in 1,613,680 control chromosomes in the GnomAD database, including 4,355 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 405 hom., cov: 33)

Exomes 𝑓: 0.052 ( 3950 hom. )

Consequence

WDR62
NM_001083961.2 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 1.38

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 19-36058782-G-A is Benign according to our data. Variant chr19-36058782-G-A is described in ClinVar as [Benign]. Clinvar id is 160258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-36058782-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR62	NM_001083961.2 link	c.180G>A	p.Val60Val	splice_region_variant, synonymous_variant	Exon 2 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.180G>A	p.Val60Val	splice_region_variant, synonymous_variant	Exon 2 of 32	1	NM_001083961.2	ENSP00000384792.1		O43379-4

Frequencies

GnomAD3 genomes

AF:

0.0497

AC:

7558

AN:

152200

Hom.:

403

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0242

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0787

Gnomad ASJ

AF:

0.0680

Gnomad EAS

AF:

0.221

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.0328

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0367

Gnomad OTH

AF:

0.0568

GnomAD3 exomes

AF:

0.0805

AC:

20196

AN:

250918

Hom.:

1433

AF XY:

0.0838

AC XY:

11372

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.0251

Gnomad AMR exome

AF:

0.100

Gnomad ASJ exome

AF:

0.0674

Gnomad EAS exome

AF:

0.221

Gnomad SAS exome

AF:

0.200

Gnomad FIN exome

AF:

0.0360

Gnomad NFE exome

AF:

0.0380

Gnomad OTH exome

AF:

0.0664

GnomAD4 exome

AF:

0.0522

AC:

76238

AN:

1461362

Hom.:

3950

Cov.:

AF XY:

0.0562

AC XY:

40832

AN XY:

727020

show subpopulations

Gnomad4 AFR exome

AF:

0.0228

Gnomad4 AMR exome

AF:

0.0977

Gnomad4 ASJ exome

AF:

0.0710

Gnomad4 EAS exome

AF:

0.209

Gnomad4 SAS exome

AF:

0.191

Gnomad4 FIN exome

AF:

0.0358

Gnomad4 NFE exome

AF:

0.0345

Gnomad4 OTH exome

AF:

0.0658

GnomAD4 genome

AF:

0.0497

AC:

7570

AN:

152318

Hom.:

405

Cov.:

AF XY:

0.0533

AC XY:

3971

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0242

Gnomad4 AMR

AF:

0.0789

Gnomad4 ASJ

AF:

0.0680

Gnomad4 EAS

AF:

0.222

Gnomad4 SAS

AF:

0.202

Gnomad4 FIN

AF:

0.0328

Gnomad4 NFE

AF:

0.0367

Gnomad4 OTH

AF:

0.0605

Alfa

AF:

0.0389

Hom.:

Bravo

AF:

0.0479

Asia WGS

AF:

0.261

AC:

907

AN:

3478

EpiCase

AF:

0.0388

EpiControl

AF:

0.0359

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

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

Significance: Benign

Review Status: no assertion criteria provided

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

- -

Jul 03, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

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

- -

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

Benign:3

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

- -

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. -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.87

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