rs12522383

Variant names:

• chr5-111119568-G-A
• rs12522383
• NM_139281.3:c.1904+448G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139281.3(WDR36):​c.1904+448G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 151,914 control chromosomes in the GnomAD database, including 6,906 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (6906 hom., cov: 32)
• Consequence: WDR36 NM_139281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR36	NM_139281.3	c.1904+448G>A		intron_variant	Intron 17 of 22	ENST00000513710.4	NP_644810.2
WDR36	XM_047416729.1	c.1904+448G>A		intron_variant	Intron 17 of 20		XP_047272685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR36	ENST00000513710.4	c.1904+448G>A		intron_variant	Intron 17 of 22	1	NM_139281.3	ENSP00000424628.3

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44761 AN: 151796 Hom.: 6905 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.309

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.295 AC: 44768 AN: 151914 Hom.: 6906 Cov.: 32 AF XY: 0.300 AC XY: 22296 AN XY: 74220

African (AFR) AF: 0.218 AC: 9050 AN: 41440

American (AMR) AF: 0.332 AC: 5070 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1332 AN: 3462

East Asian (EAS) AF: 0.254 AC: 1306 AN: 5148

South Asian (SAS) AF: 0.394 AC: 1900 AN: 4826

European-Finnish (FIN) AF: 0.408 AC: 4294 AN: 10526

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20810 AN: 67934

Other (OTH) AF: 0.307 AC: 647 AN: 2110

Alfa AF: 0.303 Hom.: 24642

Bravo AF: 0.285

Asia WGS AF: 0.300 AC: 1045 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.73
DANN	Benign	0.40
PhyloP100		-0.43
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: rs12522383; hg19: chr5-110455266;