rs17624563

chr5-111120565-C-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_139281.3(WDR36):c.1974C>G(p.Val658=) 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

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 -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 id 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/exons	MANE	UniProt
WDR36	NM_139281.3	c.1974C>G	p.Val658=	synonymous_variant	18/23	ENST00000513710.4
WDR36	XM_047416729.1	c.1974C>G	p.Val658=	synonymous_variant	18/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR36	ENST00000513710.4	c.1974C>G	p.Val658=	synonymous_variant	18/23	1	NM_139281.3	P1

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

GnomAD3 exomes AF: 0.108 AC: 27192 AN: 250744 Hom.: 1905 AF XY: 0.115 AC XY: 15622 AN XY: 135480

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 SAS exome AF: 0.234

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

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.0501

Gnomad4 ASJ exome AF: 0.0812

Gnomad4 EAS exome AF: 0.0473

Gnomad4 SAS exome AF: 0.234

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.0926

Gnomad4 OTH exome AF: 0.103

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

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.0742

Gnomad4 ASJ AF: 0.0862

Gnomad4 EAS AF: 0.0610

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.100

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

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 22, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	2.8
Dann	Benign	0.68

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