chr5-111103810-A-G

Position:

• chr5-111103810-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_139281.3(WDR36):​c.622A>G​(p.Ile208Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,610,358 control chromosomes in the GnomAD database, including 79,260 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5998 hom., cov: 32)
  • Exomes 𝑓: 0.31 (73262 hom.)
• Consequence: WDR36 NM_139281.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.267

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0010918379).
• BP6: Variant 5-111103810-A-G is Benign according to our data. Variant chr5-111103810-A-G is described in ClinVar as [Benign]. Clinvar id is 262466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-111103810-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR36	NM_139281.3	c.622A>G	p.Ile208Val	missense_variant	7/23	ENST00000513710.4	NP_644810.2
WDR36	XM_047416729.1	c.622A>G	p.Ile208Val	missense_variant	7/21		XP_047272685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR36	ENST00000513710.4	c.622A>G	p.Ile208Val	missense_variant	7/23	1	NM_139281.3	ENSP00000424628	P1
WDR36	ENST00000504122.2	n.504A>G		non_coding_transcript_exon_variant	5/5	4
WDR36	ENST00000505303.5	n.758A>G		non_coding_transcript_exon_variant	7/15	5

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39356 AN: 151428 Hom.: 6001 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.282

GnomAD3 exomes AF: 0.327 AC: 81714 AN: 249790 Hom.: 14427 AF XY: 0.332 AC XY: 44880 AN XY: 135010

Gnomad AFR exome AF: 0.0980

Gnomad AMR exome AF: 0.427

Gnomad ASJ exome AF: 0.362

Gnomad EAS exome AF: 0.246

Gnomad SAS exome AF: 0.407

Gnomad FIN exome AF: 0.394

Gnomad NFE exome AF: 0.306

Gnomad OTH exome AF: 0.326

GnomAD4 exome AF: 0.312 AC: 454687 AN: 1458812 Hom.: 73262 Cov.: 37 AF XY: 0.316 AC XY: 229002 AN XY: 725686

Gnomad4 AFR exome AF: 0.0931

Gnomad4 AMR exome AF: 0.413

Gnomad4 ASJ exome AF: 0.363

Gnomad4 EAS exome AF: 0.244

Gnomad4 SAS exome AF: 0.403

Gnomad4 FIN exome AF: 0.392

Gnomad4 NFE exome AF: 0.304

Gnomad4 OTH exome AF: 0.305

GnomAD4 genome AF: 0.260 AC: 39343 AN: 151546 Hom.: 5998 Cov.: 32 AF XY: 0.267 AC XY: 19768 AN XY: 74060

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.279

Alfa AF: 0.296 Hom.: 16918

Bravo AF: 0.247

TwinsUK AF: 0.296 AC: 1099

ALSPAC AF: 0.307 AC: 1185

ESP6500AA AF: 0.102 AC: 448

ESP6500EA AF: 0.309 AC: 2652

ExAC AF: 0.317 AC: 38486

Asia WGS AF: 0.296 AC: 1031 AN: 3476

EpiCase AF: 0.321

EpiControl AF: 0.314

ClinVar

Significance: 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	GeneDx	Jul 05, 2018	This variant is associated with the following publications: (PMID: 19150991, 17960130, 15677485) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Glaucoma 1, open angle, G Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.062
DANN	Benign	0.42
DEOGEN2	Benign	0.082	T;T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.61	.;T;T
MetaRNN	Benign	0.0011	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.48	N;N;.
MutationTaster	Benign	0.052	P;P;P
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.010	N;.;.
REVEL	Benign	0.065
Sift4G	Benign	0.97	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.041
MPC		0.026
ClinPred		0.00047	T
GERP RS		0.61
Varity_R		0.047
gMVP		0.19

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: rs11241095; hg19: chr5-110439509; COSMIC: COSV72411443;