5-111094907-C-CT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_139281.3(WDR36):c.163-7dup variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,593,906 control chromosomes in the GnomAD database, including 44 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0092 (22 hom., cov: 32)
  • Exomes 𝑓: 0.00097 (22 hom.)
• Consequence: WDR36 NM_139281.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.550

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 5-111094907-C-CT is Benign according to our data. Variant chr5-111094907-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 350301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00916 (1392/152034) while in subpopulation AFR AF= 0.0322 (1336/41474). AF 95% confidence interval is 0.0308. There are 22 homozygotes in gnomad4. There are 651 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 22 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR36	NM_139281.3	c.163-7dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000513710.4
WDR36	XM_047416729.1	c.163-7dup		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR36	ENST00000513710.4	c.163-7dup		splice_polypyrimidine_tract_variant, intron_variant		1	NM_139281.3	P1
WDR36	ENST00000505303.5	n.299-7dup		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5
WDR36	ENST00000515784.1	n.273-7dup		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00914 AC: 1388 AN: 151916 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.0322

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00384

GnomAD3 exomes AF: 0.00247 AC: 569 AN: 230590 Hom.: 9 AF XY: 0.00179 AC XY: 222 AN XY: 124280

Gnomad AFR exome AF: 0.0319

Gnomad AMR exome AF: 0.00234

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000701

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000395

Gnomad OTH exome AF: 0.00192

GnomAD4 exome AF: 0.000967 AC: 1395 AN: 1441872 Hom.: 22 Cov.: 29 AF XY: 0.000808 AC XY: 579 AN XY: 716606

Gnomad4 AFR exome AF: 0.0333

Gnomad4 AMR exome AF: 0.00254

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000356

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.0000455

Gnomad4 OTH exome AF: 0.00205

GnomAD4 genome AF: 0.00916 AC: 1392 AN: 152034 Hom.: 22 Cov.: 32 AF XY: 0.00876 AC XY: 651 AN XY: 74316

Gnomad4 AFR AF: 0.0322

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000442

Gnomad4 OTH AF: 0.00380

Alfa AF: 0.00518 Hom.: 1

Bravo AF: 0.0107

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 16, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 25, 2019	- -

WDR36-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 06, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Primary open angle glaucoma Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs201659734; hg19: chr5-110430605;