rs34962120

Variant names:

• chr5-111110392-G-A
• rs34962120
• NM_139281.3:c.1441+89G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_139281.3(WDR36):​c.1441+89G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,087,124 control chromosomes in the GnomAD database, including 53,599 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (5953 hom., cov: 32)
  • Exomes 𝑓: 0.31 (47646 hom.)
• Consequence: WDR36 NM_139281.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.100
• Publications: 4 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-111110392-G-A is Benign according to our data. Variant chr5-111110392-G-A is described in ClinVar as Benign. ClinVar VariationId is 1237247.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR36	NM_139281.3	c.1441+89G>A		intron_variant	Intron 13 of 22	ENST00000513710.4	NP_644810.2
WDR36	XM_047416729.1	c.1441+89G>A		intron_variant	Intron 13 of 20		XP_047272685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR36	ENST00000513710.4	c.1441+89G>A		intron_variant	Intron 13 of 22	1	NM_139281.3	ENSP00000424628.3
WDR36	ENST00000505303.5	n.1577+89G>A		intron_variant	Intron 13 of 14	5

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39206 AN: 151076 Hom.: 5956 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.310 AC: 290138 AN: 935932 Hom.: 47646 AF XY: 0.315 AC XY: 153291 AN XY: 486640

African (AFR) AF: 0.0949 AC: 2105 AN: 22186

American (AMR) AF: 0.413 AC: 17170 AN: 41586

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 8191 AN: 22532

East Asian (EAS) AF: 0.240 AC: 8473 AN: 35320

South Asian (SAS) AF: 0.400 AC: 29475 AN: 73610

European-Finnish (FIN) AF: 0.392 AC: 18785 AN: 47948

Middle Eastern (MID) AF: 0.401 AC: 1585 AN: 3956

European-Non Finnish (NFE) AF: 0.296 AC: 191467 AN: 645894

Other (OTH) AF: 0.300 AC: 12887 AN: 42900

GnomAD4 genome AF: 0.259 AC: 39189 AN: 151192 Hom.: 5953 Cov.: 32 AF XY: 0.267 AC XY: 19693 AN XY: 73860

African (AFR) AF: 0.100 AC: 4152 AN: 41414

American (AMR) AF: 0.323 AC: 4874 AN: 15098

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1217 AN: 3452

East Asian (EAS) AF: 0.253 AC: 1301 AN: 5150

South Asian (SAS) AF: 0.391 AC: 1879 AN: 4802

European-Finnish (FIN) AF: 0.406 AC: 4282 AN: 10538

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

European-Non Finnish (NFE) AF: 0.305 AC: 20543 AN: 67440

Other (OTH) AF: 0.277 AC: 580 AN: 2092

Alfa AF: 0.263 Hom.: 777

Bravo AF: 0.246

Asia WGS AF: 0.288 AC: 1001 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 26, 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	-0.91
CADD	Benign	7.5
DANN	Benign	0.51
PhyloP100		-0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	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: rs34962120; hg19: chr5-110446091; COSMIC: COSV72605347;