5-111119021-A-G

Position:

chr5-111119021-A-G

Variant summary

Our verdict is Benign. Variant got -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 (★★).

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, BayesDel_noAF, Cadd, Eigen, MutationAssessor, phyloP100way_vertebrate, PROVEAN, 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 [Likely_benign]. Clinvar id is 1580.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-111119021-A-G is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR36	NM_139281.3 linkuse as main transcript	c.1805A>G	p.Asp602Gly	missense_variant	17/23	ENST00000513710.4	NP_644810.2
WDR36	XM_047416729.1 linkuse as main transcript	c.1805A>G	p.Asp602Gly	missense_variant	17/21		XP_047272685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR36	ENST00000513710.4 linkuse as main transcript	c.1805A>G	p.Asp602Gly	missense_variant	17/23	1	NM_139281.3	ENSP00000424628	P1

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

GnomAD3 exomes

AF:

0.00430

AC:

1080

AN:

250978

Hom.:

AF XY:

0.00441

AC XY:

598

AN XY:

135626

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 SAS exome

AF:

0.000784

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

Gnomad4 AFR exome

AF:

0.00132

Gnomad4 AMR exome

AF:

0.00414

Gnomad4 ASJ exome

AF:

0.00724

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000719

Gnomad4 FIN exome

AF:

0.00157

Gnomad4 NFE exome

AF:

0.00784

Gnomad4 OTH exome

AF:

0.00638

GnomAD4 genome

AF:

0.00459

AC:

698

AN:

152220

Hom.:

Cov.:

AF XY:

0.00425

AC XY:

316

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00152

Gnomad4 AMR

AF:

0.00707

Gnomad4 ASJ

AF:

0.00866

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.00676

Gnomad4 OTH

AF:

0.00853

Alfa

AF:

0.00724

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

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	WDR36: BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 11, 2023	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Glaucoma 1, open angle, G

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Jan 01, 2008

- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

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;.

MutationTaster

Benign

1.0

A;A

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over