5-111124249-G-C

Position:

• chr5-111124249-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_139281.3(WDR36):​c.2350+60G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0867 in 1,358,618 control chromosomes in the GnomAD database, including 6,643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.089 (644 hom., cov: 32)
  • Exomes 𝑓: 0.086 (5999 hom.)
• Consequence: WDR36 NM_139281.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.310

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-111124249-G-C is Benign according to our data. Variant chr5-111124249-G-C is described in ClinVar as [Benign]. Clinvar id is 1250176.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR36	NM_139281.3	c.2350+60G>C		intron_variant		ENST00000513710.4	NP_644810.2
WDR36	XM_047416729.1	c.2268+325G>C		intron_variant			XP_047272685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR36	ENST00000513710.4	c.2350+60G>C		intron_variant		1	NM_139281.3	ENSP00000424628	P1

Frequencies

GnomAD3 genomes AF: 0.0894 AC: 13577 AN: 151906 Hom.: 643 Cov.: 32

Gnomad AFR AF: 0.0858

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0609

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.0606

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.0983

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0907

Gnomad OTH AF: 0.0789

GnomAD4 exome AF: 0.0864 AC: 104230 AN: 1206594 Hom.: 5999 AF XY: 0.0919 AC XY: 55851 AN XY: 607918

Gnomad4 AFR exome AF: 0.0867

Gnomad4 AMR exome AF: 0.0428

Gnomad4 ASJ exome AF: 0.0691

Gnomad4 EAS exome AF: 0.0448

Gnomad4 SAS exome AF: 0.230

Gnomad4 FIN exome AF: 0.0930

Gnomad4 NFE exome AF: 0.0783

Gnomad4 OTH exome AF: 0.0858

GnomAD4 genome AF: 0.0893 AC: 13583 AN: 152024 Hom.: 644 Cov.: 32 AF XY: 0.0921 AC XY: 6842 AN XY: 74288

Gnomad4 AFR AF: 0.0857

Gnomad4 AMR AF: 0.0608

Gnomad4 ASJ AF: 0.0749

Gnomad4 EAS AF: 0.0607

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.0983

Gnomad4 NFE AF: 0.0906

Gnomad4 OTH AF: 0.0800

Alfa AF: 0.0584 Hom.: 63

Bravo AF: 0.0797

Asia WGS AF: 0.145 AC: 501 AN: 3446

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 07, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.5
DANN	Benign	0.74

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: rs2290680; hg19: chr5-110459947; COSMIC: COSV72605392;