Variant rs11956837 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_139281.3(WDR36):c.1843A>G(p.Met615Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0043 in 1,613,560 control chromosomes in the GnomAD database, including 260 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 133 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 127 hom. )

Consequence

WDR36
NM_139281.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.76

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024859607).

BP6

Variant 5-111119059-A-G is Benign according to our data. Variant chr5-111119059-A-G is described in ClinVar as [Benign]. Clinvar id is 350330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR36	NM_139281.3 link	c.1843A>G	p.Met615Val	missense_variant	17/23	ENST00000513710.4	NP_644810.2	Q8NI36
WDR36	XM_047416729.1 link	c.1843A>G	p.Met615Val	missense_variant	17/21		XP_047272685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR36	ENST00000513710.4 link	c.1843A>G	p.Met615Val	missense_variant	17/23	1	NM_139281.3	ENSP00000424628.3		A0A0A0MTB8

Frequencies

GnomAD3 genomes

AF:

0.0229

AC:

3483

AN:

152080

Hom.:

133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0799

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00819

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.0143

GnomAD3 exomes

AF:

0.00600

AC:

1507

AN:

251054

Hom.:

AF XY:

0.00433

AC XY:

588

AN XY:

135668

show subpopulations

Gnomad AFR exome

AF:

0.0797

Gnomad AMR exome

AF:

0.00486

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00237

AC:

3459

AN:

1461362

Hom.:

127

Cov.:

AF XY:

0.00204

AC XY:

1482

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.0830

Gnomad4 AMR exome

AF:

0.00528

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000981

Gnomad4 OTH exome

AF:

0.00494

GnomAD4 genome

AF:

0.0229

AC:

3483

AN:

152198

Hom.:

133

Cov.:

AF XY:

0.0226

AC XY:

1683

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0797

Gnomad4 AMR

AF:

0.00818

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00478

Hom.:

Bravo

AF:

0.0257

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0752

AC:

331

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00731

AC:

888

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 17, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.22

T;T;T

Eigen

Benign

-0.020

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.76

.;T;T

MetaRNN

Benign

0.0025

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.7

L;L;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-2.0

N;.;.

REVEL

Uncertain

0.31

Sift4G

Benign

0.12

T;T;T

Polyphen

0.0060

B;B;.

Vest4

0.44

MVP

0.69

MPC

0.030

ClinPred

0.022

GERP RS

4.9

Varity_R

0.55

gMVP

0.46

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

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