rs34595252

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3BP4_StrongBP6_Very_StrongBS2

The NM_139281.3(WDR36):c.1805A>G(p.Asp602Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00644 in 1,612,732 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D602H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0046 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0066 ( 33 hom. )

Consequence

WDR36
NM_139281.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:4

Conservation

PhyloP100: 8.04

Publications

43 publications found

Variant links:

Genes affected

WDR36 (HGNC:30696): (WD repeat domain 36) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Mutations in this gene have been associated with adult-onset primary open-angle glaucoma (POAG). [provided by RefSeq, Jul 2008]

WDR36 Gene-Disease associations (from GenCC):

glaucoma 1, open angle, G
Inheritance: Unknown, AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

WDR36 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 9: AlphaMissense, BayesDel_noAF, Cadd, Eigen, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.051918864).

BP6

Variant 5-111119021-A-G is Benign according to our data. Variant chr5-111119021-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1580.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 698 Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR36	NM_139281.3 link	c.1805A>G	p.Asp602Gly	missense_variant	Exon 17 of 23	ENST00000513710.4	NP_644810.2	Q8NI36
WDR36	XM_047416729.1 link	c.1805A>G	p.Asp602Gly	missense_variant	Exon 17 of 21		XP_047272685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR36	ENST00000513710.4 link	c.1805A>G	p.Asp602Gly	missense_variant	Exon 17 of 23	1	NM_139281.3	ENSP00000424628.3		A0A0A0MTB8

Frequencies

GnomAD3 genomes

AF:

0.00459

AC:

698

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00708

Gnomad ASJ

AF:

0.00866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00676

Gnomad OTH

AF:

0.00862

GnomAD2 exomes

AF:

0.00430

AC:

1080

AN:

250978

AF XY:

0.00441

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00387

Gnomad ASJ exome

AF:

0.00635

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000786

Gnomad NFE exome

AF:

0.00697

Gnomad OTH exome

AF:

0.00589

GnomAD4 exome

AF:

0.00664

AC:

9694

AN:

1460512

Hom.:

Cov.:

AF XY:

0.00658

AC XY:

4784

AN XY:

726648

show subpopulations

African (AFR)

AF:

0.00132

AC:

AN:

33438

American (AMR)

AF:

0.00414

AC:

185

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00724

AC:

189

AN:

26114

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39652

South Asian (SAS)

AF:

0.000719

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00157

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00642

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00784

AC:

8706

AN:

1110888

Other (OTH)

AF:

0.00638

AC:

385

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

470

941

1411

1882

2352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

330

660

990

1320

1650

<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:

0.00459

AC:

698

AN:

152220

Hom.:

Cov.:

AF XY:

0.00425

AC XY:

316

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.00152

AC:

AN:

41550

American (AMR)

AF:

0.00707

AC:

108

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00866

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00145

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000660

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00676

AC:

460

AN:

68010

Other (OTH)

AF:

0.00853

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

103

137

171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00707

Hom.:

Bravo

AF:

0.00557

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00721

AC:

ExAC

AF:

0.00421

AC:

511

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00851

EpiControl

AF:

0.00794

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 11, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

WDR36: BS2 -

Glaucoma 1, open angle, G

Uncertain:1

Jan 01, 2008

OMIM

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Pathogenic

0.41

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;D;T

Eigen

Pathogenic

0.97

Eigen_PC

Pathogenic

0.91

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

.;D;D

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.052

T;T;T

MetaSVM

Uncertain

0.63

MutationAssessor

Pathogenic

4.0

H;H;.

PhyloP100

8.0

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-6.4

D;.;.

REVEL

Pathogenic

0.93

Sift4G

Uncertain

0.014

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.84

MVP

0.95

MPC

0.25

ClinPred

0.16

GERP RS

6.1

Varity_R

0.67

gMVP

0.73

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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