Genetic Variant WDR36:c.1326+90C>T (chr5-111107529-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_139281.3(WDR36):c.1326+90C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 1,517,830 control chromosomes in the GnomAD database, including 180,361 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.54 ( 22693 hom., cov: 32)

Exomes 𝑓: 0.47 ( 157668 hom. )

Consequence

WDR36
NM_139281.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.180

Publications

10 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR36	NM_139281.3 link	c.1326+90C>T		intron_variant	Intron 12 of 22	ENST00000513710.4	NP_644810.2
WDR36	XM_047416729.1 link	c.1326+90C>T		intron_variant	Intron 12 of 20		XP_047272685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR36	ENST00000513710.4 link	c.1326+90C>T		intron_variant	Intron 12 of 22	1	NM_139281.3	ENSP00000424628.3
WDR36	ENST00000505303.5 link	n.1462+90C>T		intron_variant	Intron 12 of 14	5

Frequencies

GnomAD3 genomes

AF:

0.538

AC:

81212

AN:

150958

Hom.:

22662

Cov.:

show subpopulations

Gnomad AFR

AF:

0.671

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.546

Gnomad ASJ

AF:

0.492

Gnomad EAS

AF:

0.394

Gnomad SAS

AF:

0.680

Gnomad FIN

AF:

0.549

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.458

Gnomad OTH

AF:

0.528

GnomAD4 exome

AF:

0.474

AC:

647377

AN:

1366754

Hom.:

157668

AF XY:

0.479

AC XY:

325749

AN XY:

679524

show subpopulations

African (AFR)

AF:

0.677

AC:

20835

AN:

30778

American (AMR)

AF:

0.623

AC:

23316

AN:

37438

Ashkenazi Jewish (ASJ)

AF:

0.495

AC:

12210

AN:

24652

East Asian (EAS)

AF:

0.361

AC:

13680

AN:

37932

South Asian (SAS)

AF:

0.678

AC:

53263

AN:

78564

European-Finnish (FIN)

AF:

0.528

AC:

24079

AN:

45624

Middle Eastern (MID)

AF:

0.605

AC:

2559

AN:

4232

European-Non Finnish (NFE)

AF:

0.447

AC:

469781

AN:

1050828

Other (OTH)

AF:

0.488

AC:

27654

AN:

56706

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

15861

31722

47583

63444

79305

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14336

28672

43008

57344

71680

<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:

0.538

AC:

81299

AN:

151076

Hom.:

22693

Cov.:

AF XY:

0.544

AC XY:

40160

AN XY:

73838

show subpopulations

African (AFR)

AF:

0.672

AC:

27757

AN:

41332

American (AMR)

AF:

0.546

AC:

8263

AN:

15126

Ashkenazi Jewish (ASJ)

AF:

0.492

AC:

1695

AN:

3446

East Asian (EAS)

AF:

0.395

AC:

2032

AN:

5150

South Asian (SAS)

AF:

0.680

AC:

3280

AN:

4820

European-Finnish (FIN)

AF:

0.549

AC:

5794

AN:

10552

Middle Eastern (MID)

AF:

0.633

AC:

186

AN:

294

European-Non Finnish (NFE)

AF:

0.458

AC:

30855

AN:

67350

Other (OTH)

AF:

0.527

AC:

1104

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1856

3711

5567

7422

9278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

708

1416

2124

2832

3540

<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:

0.519

Hom.:

2810

Bravo

AF:

0.536

Asia WGS

AF:

0.530

AC:

1845

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.7

(source)

DANN

Benign

0.25

PhyloP100

-0.18

Mutation Taster

=100/0

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

Computational scores

Splicing

Publications

Other links and lift over