NM_001083961.2:c.4123G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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

Publications

16 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 -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 VariationId is 160298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
WDR62	NM_001083961.2 link	c.4123G>A	p.Gly1375Ser	missense_variant	Exon 30 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.4123G>A	p.Gly1375Ser	missense_variant	Exon 30 of 32	1	NM_001083961.2	ENSP00000384792.1

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

GnomAD2 exomes

AF:

0.0380

AC:

9043

AN:

237866

AF XY:

0.0393

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 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

African (AFR)

AF:

0.00783

AC:

262

AN:

33456

American (AMR)

AF:

0.0299

AC:

1335

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0559

AC:

1460

AN:

26134

East Asian (EAS)

AF:

0.000101

AC:

AN:

39696

South Asian (SAS)

AF:

0.0224

AC:

1933

AN:

86224

European-Finnish (FIN)

AF:

0.0459

AC:

1766

AN:

38466

Middle Eastern (MID)

AF:

0.0668

AC:

361

AN:

5408

European-Non Finnish (NFE)

AF:

0.0490

AC:

54433

AN:

1111884

Other (OTH)

AF:

0.0438

AC:

2638

AN:

60254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

4075

8150

12224

16299

20374

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1928

3856

5784

7712

9640

<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:

0.0350

AC:

5338

AN:

152302

Hom.:

140

Cov.:

AF XY:

0.0349

AC XY:

2599

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.00864

AC:

359

AN:

41562

American (AMR)

AF:

0.0373

AC:

571

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0625

AC:

217

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.0216

AC:

104

AN:

4824

European-Finnish (FIN)

AF:

0.0486

AC:

516

AN:

10624

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0497

AC:

3380

AN:

68024

Other (OTH)

AF:

0.0487

AC:

103

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

267

535

802

1070

1337

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.0462

Hom.:

184

Bravo

AF:

0.0345

TwinsUK

AF:

0.0461

AC:

171

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

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

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

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.

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

Jan 30, 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

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.054

(source)

DANN

Benign

0.36

DEOGEN2

Benign

0.0

.;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

LIST_S2

Benign

0.35

T;T

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N

PhyloP100

0.030

PrimateAI

Benign

0.30

PROVEAN

Benign

1.3

N;N

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Vest4

0.022

ClinPred

0.0000096

GERP RS

-1.6

Varity_R

0.033

gMVP

0.097

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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