NM_001083961.2:c.1641G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001083961.2(WDR62):c.1641G>A(p.Thr547Thr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,612,594 control chromosomes in the GnomAD database, including 30,757 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T547T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.15 ( 2170 hom., cov: 31)

Exomes 𝑓: 0.19 ( 28587 hom. )

Consequence

WDR62
NM_001083961.2 splice_region, synonymous

Scores

Splicing: ADA: 0.00002623

Clinical Significance

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

Conservation

PhyloP100: -1.64

Publications

21 publications found

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 Gene-Disease associations (from GenCC):

microcephaly 2, primary, autosomal recessive, with or without cortical malformations
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, Illumina, G2P, ClinGen
autosomal recessive primary microcephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

WDR62 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 19-36084743-G-A is Benign according to our data. Variant chr19-36084743-G-A is described in ClinVar as Benign. ClinVar VariationId is 160252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.64 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR62	NM_001083961.2 link	c.1641G>A	p.Thr547Thr	splice_region_variant, synonymous_variant	Exon 12 of 32	ENST00000401500.7	NP_001077430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR62	ENST00000401500.7 link	c.1641G>A	p.Thr547Thr	splice_region_variant, synonymous_variant	Exon 12 of 32	1	NM_001083961.2	ENSP00000384792.1

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22814

AN:

151936

Hom.:

2169

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0378

Gnomad AMI

AF:

0.229

Gnomad AMR

AF:

0.157

Gnomad ASJ

AF:

0.229

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.157

GnomAD2 exomes

AF:

0.180

AC:

44946

AN:

250222

AF XY:

0.185

show subpopulations

Gnomad AFR exome

AF:

0.0350

Gnomad AMR exome

AF:

0.150

Gnomad ASJ exome

AF:

0.223

Gnomad EAS exome

AF:

0.194

Gnomad FIN exome

AF:

0.167

Gnomad NFE exome

AF:

0.205

Gnomad OTH exome

AF:

0.198

GnomAD4 exome

AF:

0.195

AC:

284616

AN:

1460538

Hom.:

28587

Cov.:

AF XY:

0.195

AC XY:

141911

AN XY:

726518

show subpopulations

African (AFR)

AF:

0.0318

AC:

1065

AN:

33476

American (AMR)

AF:

0.150

AC:

6693

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

5999

AN:

26134

East Asian (EAS)

AF:

0.177

AC:

7035

AN:

39696

South Asian (SAS)

AF:

0.182

AC:

15661

AN:

86230

European-Finnish (FIN)

AF:

0.171

AC:

9017

AN:

52612

Middle Eastern (MID)

AF:

0.229

AC:

1302

AN:

5676

European-Non Finnish (NFE)

AF:

0.204

AC:

226232

AN:

1111644

Other (OTH)

AF:

0.192

AC:

11612

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

12031

24062

36093

48124

60155

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7736

15472

23208

30944

38680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.150

AC:

22812

AN:

152056

Hom.:

2170

Cov.:

AF XY:

0.149

AC XY:

11071

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.0377

AC:

1564

AN:

41508

American (AMR)

AF:

0.157

AC:

2397

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

794

AN:

3466

East Asian (EAS)

AF:

0.182

AC:

937

AN:

5146

South Asian (SAS)

AF:

0.169

AC:

815

AN:

4816

European-Finnish (FIN)

AF:

0.160

AC:

1689

AN:

10572

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.206

AC:

14018

AN:

67968

Other (OTH)

AF:

0.158

AC:

333

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

927

1853

2780

3706

4633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

256

512

768

1024

1280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.184

Hom.:

8248

Bravo

AF:

0.145

Asia WGS

AF:

0.161

AC:

561

AN:

3478

EpiCase

AF:

0.206

EpiControl

AF:

0.212

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 17, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

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 09, 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 13, 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

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 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

-0.77

CADD

Benign

1.1

(source)

DANN

Benign

0.72

PhyloP100

-1.6

PromoterAI

0.061

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Mutation Taster

=66/34

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000026

dbscSNV1_RF

Benign

0.018

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over