rs11956837

Variant names:

• chr5-111119059-A-G
• rs11956837
• NM_139281.3:c.1843A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000513710.4(WDR36):​c.1843A>G​(p.Met615Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0043 in 1,613,560 control chromosomes in the GnomAD database, including 260 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (133 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (127 hom.)
• Consequence: WDR36 ENST00000513710.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.76
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024859607).
• BP6: Variant 5-111119059-A-G is Benign according to our data. Variant chr5-111119059-A-G is described in ClinVar as Benign. ClinVar VariationId is 350330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0774 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000513710.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR36	NM_139281.3	MANE Select	c.1843A>G	p.Met615Val	missense	Exon 17 of 23	NP_644810.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR36	ENST00000513710.4	TSL:1 MANE Select	c.1843A>G	p.Met615Val	missense	Exon 17 of 23	ENSP00000424628.3

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3483 AN: 152080 Hom.: 133 Cov.: 32

Gnomad AFR AF: 0.0799

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00819

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0143

GnomAD2 exomes AF: 0.00600 AC: 1507 AN: 251054 AF XY: 0.00433

Gnomad AFR exome AF: 0.0797

Gnomad AMR exome AF: 0.00486

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00237 AC: 3459 AN: 1461362 Hom.: 127 Cov.: 31 AF XY: 0.00204 AC XY: 1482 AN XY: 727004

African (AFR) AF: 0.0830 AC: 2775 AN: 33442

American (AMR) AF: 0.00528 AC: 236 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000191 AC: 5 AN: 26116

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39666

South Asian (SAS) AF: 0.000278 AC: 24 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5762

European-Non Finnish (NFE) AF: 0.0000981 AC: 109 AN: 1111630

Other (OTH) AF: 0.00494 AC: 298 AN: 60372

GnomAD4 genome AF: 0.0229 AC: 3483 AN: 152198 Hom.: 133 Cov.: 32 AF XY: 0.0226 AC XY: 1683 AN XY: 74420

African (AFR) AF: 0.0797 AC: 3309 AN: 41518

American (AMR) AF: 0.00818 AC: 125 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 67992

Other (OTH) AF: 0.0142 AC: 30 AN: 2114

Alfa AF: 0.0112 Hom.: 134

Bravo AF: 0.0257

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0752 AC: 331

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00731 AC: 888

Asia WGS AF: 0.00404 AC: 16 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.020
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.8
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.31
Sift4G	Benign	0.12	T
Polyphen		0.0060	B
Vest4		0.44
MVP		0.69
MPC		0.030
ClinPred		0.022	T
GERP RS		4.9
Varity_R		0.55
gMVP		0.46
Mutation Taster		=87/13	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: rs11956837; hg19: chr5-110454757;