rs17624563

Variant names:

• chr5-111120565-C-G
• rs17624563
• NM_139281.3:c.1974C>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_139281.3(WDR36):​c.1974C>G​(p.Val658Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,611,152 control chromosomes in the GnomAD database, including 9,763 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (946 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8817 hom.)
• Consequence: WDR36 NM_139281.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.109
• Publications: 20 publications found

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 5-111120565-C-G is Benign according to our data. Variant chr5-111120565-C-G is described in ClinVar as Benign. ClinVar VariationId is 1222170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.109 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR36	NM_139281.3	c.1974C>G	p.Val658Val	synonymous_variant	Exon 18 of 23	ENST00000513710.4	NP_644810.2
WDR36	XM_047416729.1	c.1974C>G	p.Val658Val	synonymous_variant	Exon 18 of 21		XP_047272685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR36	ENST00000513710.4	c.1974C>G	p.Val658Val	synonymous_variant	Exon 18 of 23	1	NM_139281.3	ENSP00000424628.3

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16417 AN: 151968 Hom.: 945 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0744

Gnomad ASJ AF: 0.0862

Gnomad EAS AF: 0.0608

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0991

GnomAD2 exomes AF: 0.108 AC: 27192 AN: 250744 AF XY: 0.115

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.0470

Gnomad ASJ exome AF: 0.0799

Gnomad EAS exome AF: 0.0715

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.100

Gnomad OTH exome AF: 0.0996

GnomAD4 exome AF: 0.0999 AC: 145779 AN: 1459066 Hom.: 8817 Cov.: 31 AF XY: 0.104 AC XY: 75807 AN XY: 725960

African (AFR) AF: 0.125 AC: 4168 AN: 33356

American (AMR) AF: 0.0501 AC: 2239 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0812 AC: 2119 AN: 26090

East Asian (EAS) AF: 0.0473 AC: 1873 AN: 39572

South Asian (SAS) AF: 0.234 AC: 20131 AN: 86152

European-Finnish (FIN) AF: 0.105 AC: 5614 AN: 53308

Middle Eastern (MID) AF: 0.114 AC: 658 AN: 5758

European-Non Finnish (NFE) AF: 0.0926 AC: 102741 AN: 1109818

Other (OTH) AF: 0.103 AC: 6236 AN: 60298

GnomAD4 genome AF: 0.108 AC: 16425 AN: 152086 Hom.: 946 Cov.: 32 AF XY: 0.110 AC XY: 8205 AN XY: 74350

African (AFR) AF: 0.121 AC: 5027 AN: 41496

American (AMR) AF: 0.0742 AC: 1133 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0862 AC: 299 AN: 3470

East Asian (EAS) AF: 0.0610 AC: 316 AN: 5182

South Asian (SAS) AF: 0.239 AC: 1150 AN: 4820

European-Finnish (FIN) AF: 0.111 AC: 1171 AN: 10576

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7049 AN: 67956

Other (OTH) AF: 0.100 AC: 211 AN: 2110

Alfa AF: 0.106 Hom.: 304

Bravo AF: 0.0990

Asia WGS AF: 0.155 AC: 540 AN: 3474

EpiCase AF: 0.0973

EpiControl AF: 0.0929

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	2.8
DANN	Benign	0.68
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17624563; hg19: chr5-110456263; COSMIC: COSV72605574;