5-111103810-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_139281.3(WDR36):c.622A>G(p.Ile208Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,610,358 control chromosomes in the GnomAD database, including 79,260 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 0.26 ( 5998 hom., cov: 32)

Exomes 𝑓: 0.31 ( 73262 hom. )

Consequence

WDR36
NM_139281.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.267

Publications

51 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0010918379).

BP6

Variant 5-111103810-A-G is Benign according to our data. Variant chr5-111103810-A-G is described in ClinVar as Benign. ClinVar VariationId is 262466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR36	NM_139281.3 link	c.622A>G	p.Ile208Val	missense_variant	Exon 7 of 23	ENST00000513710.4	NP_644810.2	Q8NI36
WDR36	XM_047416729.1 link	c.622A>G	p.Ile208Val	missense_variant	Exon 7 of 21		XP_047272685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
WDR36	ENST00000513710.4 link	c.622A>G	p.Ile208Val	missense_variant	Exon 7 of 23	1	NM_139281.3	ENSP00000424628.3	A0A0A0MTB8
WDR36	ENST00000504122.2 link	n.504A>G		non_coding_transcript_exon_variant	Exon 5 of 5	4
WDR36	ENST00000505303.5 link	n.758A>G		non_coding_transcript_exon_variant	Exon 7 of 15	5

Frequencies

GnomAD3 genomes

AF:

0.260

AC:

39356

AN:

151428

Hom.:

6001

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.256

Gnomad AMR

AF:

0.323

Gnomad ASJ

AF:

0.353

Gnomad EAS

AF:

0.257

Gnomad SAS

AF:

0.393

Gnomad FIN

AF:

0.407

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.282

GnomAD2 exomes

AF:

0.327

AC:

81714

AN:

249790

AF XY:

0.332

show subpopulations

Gnomad AFR exome

AF:

0.0980

Gnomad AMR exome

AF:

0.427

Gnomad ASJ exome

AF:

0.362

Gnomad EAS exome

AF:

0.246

Gnomad FIN exome

AF:

0.394

Gnomad NFE exome

AF:

0.306

Gnomad OTH exome

AF:

0.326

GnomAD4 exome

AF:

0.312

AC:

454687

AN:

1458812

Hom.:

73262

Cov.:

AF XY:

0.316

AC XY:

229002

AN XY:

725686

show subpopulations

African (AFR)

AF:

0.0931

AC:

3105

AN:

33340

American (AMR)

AF:

0.413

AC:

18379

AN:

44486

Ashkenazi Jewish (ASJ)

AF:

0.363

AC:

9441

AN:

26024

East Asian (EAS)

AF:

0.244

AC:

9655

AN:

39614

South Asian (SAS)

AF:

0.403

AC:

34673

AN:

86128

European-Finnish (FIN)

AF:

0.392

AC:

20892

AN:

53340

Middle Eastern (MID)

AF:

0.399

AC:

2292

AN:

5746

European-Non Finnish (NFE)

AF:

0.304

AC:

337894

AN:

1109936

Other (OTH)

AF:

0.305

AC:

18356

AN:

60198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

15950

31900

47850

63800

79750

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11154

22308

33462

44616

55770

<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:

0.260

AC:

39343

AN:

151546

Hom.:

5998

Cov.:

AF XY:

0.267

AC XY:

19768

AN XY:

74060

show subpopulations

African (AFR)

AF:

0.101

AC:

4172

AN:

41474

American (AMR)

AF:

0.323

AC:

4887

AN:

15152

Ashkenazi Jewish (ASJ)

AF:

0.353

AC:

1220

AN:

3458

East Asian (EAS)

AF:

0.257

AC:

1323

AN:

5142

South Asian (SAS)

AF:

0.393

AC:

1891

AN:

4812

European-Finnish (FIN)

AF:

0.407

AC:

4294

AN:

10550

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.305

AC:

20611

AN:

67654

Other (OTH)

AF:

0.279

AC:

586

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1410

2821

4231

5642

7052

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

424

848

1272

1696

2120

<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:

0.289

Hom.:

22859

Bravo

AF:

0.247

TwinsUK

AF:

0.296

AC:

1099

ALSPAC

AF:

0.307

AC:

1185

ESP6500AA

AF:

0.102

AC:

448

ESP6500EA

AF:

0.309

AC:

2652

ExAC

AF:

0.317

AC:

38486

Asia WGS

AF:

0.296

AC:

1031

AN:

3476

EpiCase

AF:

0.321

EpiControl

AF:

0.314

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 19150991, 17960130, 15677485) -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Glaucoma 1, open angle, G

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.062

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.082

T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.61

.;T;T

MetaRNN

Benign

0.0011

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.48

N;N;.

PhyloP100

0.27

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.010

N;.;.

REVEL

Benign

0.065

Sift4G

Benign

0.97

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.041

MPC

0.026

ClinPred

0.00047

GERP RS

0.61

Varity_R

0.047

gMVP

0.19

Mutation Taster

=99/1

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