19-36103502-G-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.3674G>A(p.Arg1225His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00404 in 1,614,042 control chromosomes in the GnomAD database, including 214 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 0.020 ( 100 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 114 hom. )

Consequence

WDR62
NM_001083961.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.07

Publications

6 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), Illumina, Ambry Genetics, Laboratory for Molecular Medicine, 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=0.0013718009).

BP6

Variant 19-36103502-G-A is Benign according to our data. Variant chr19-36103502-G-A is described in ClinVar as Benign. ClinVar VariationId is 160295.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.069 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083961.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDR62	NM_001083961.2	MANE Select	c.3674G>A	p.Arg1225His	missense	Exon 30 of 32	NP_001077430.1	O43379-4
WDR62	NM_001411145.1		c.3659G>A	p.Arg1220His	missense	Exon 30 of 32	NP_001398074.1	A0A7P0TAK3
WDR62	NM_173636.5		c.3659G>A	p.Arg1220His	missense	Exon 30 of 32	NP_775907.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDR62	ENST00000401500.7	TSL:1 MANE Select	c.3674G>A	p.Arg1225His	missense	Exon 30 of 32	ENSP00000384792.1	O43379-4
WDR62	ENST00000587391.6	TSL:1	n.*3534G>A		non_coding_transcript_exon	Exon 28 of 30	ENSP00000465525.1	O43379-2
WDR62	ENST00000587391.6	TSL:1	n.*3534G>A		3_prime_UTR	Exon 28 of 30	ENSP00000465525.1	O43379-2

Frequencies

GnomAD3 genomes

AF:

0.0205

AC:

3116

AN:

152074

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0714

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00714

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0134

GnomAD2 exomes

AF:

0.00533

AC:

1341

AN:

251370

AF XY:

0.00406

show subpopulations

Gnomad AFR exome

AF:

0.0721

Gnomad AMR exome

AF:

0.00333

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000369

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00233

AC:

3405

AN:

1461850

Hom.:

114

Cov.:

AF XY:

0.00200

AC XY:

1456

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.0755

AC:

2528

AN:

33480

American (AMR)

AF:

0.00376

AC:

168

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000383

AC:

426

AN:

1112010

Other (OTH)

AF:

0.00439

AC:

265

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

257

514

771

1028

1285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

258

344

430

<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:

0.0205

AC:

3114

AN:

152192

Hom.:

100

Cov.:

AF XY:

0.0200

AC XY:

1490

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0711

AC:

2953

AN:

41508

American (AMR)

AF:

0.00713

AC:

109

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000194

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

68010

Other (OTH)

AF:

0.0133

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

156

312

467

623

779

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.00818

Hom.:

Bravo

AF:

0.0230

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0715

AC:

315

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00666

AC:

809

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

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

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.030

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.0023

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

-1.1

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.50

REVEL

Benign

0.051

Sift

Benign

0.48

Sift4G

Benign

0.21

Polyphen

0.0020

Vest4

0.022

MVP

0.24

MPC

0.27

ClinPred

0.0029

GERP RS

-9.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.020

gMVP

0.35

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over