rs2240147

Positions:

• chr19-989730-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024100.4(WDR18):​c.322-32C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,611,066 control chromosomes in the GnomAD database, including 11,487 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 0.089 (769 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10718 hom.)
• Consequence: WDR18 NM_024100.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234

Genes affected

WDR18 (HGNC:17956): (WD repeat domain 18) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR18	NM_024100.4	c.322-32C>A		intron_variant		ENST00000585809.6
WDR18	NM_001372085.1	c.322-32C>A		intron_variant
WDR18	NM_001372086.1	c.91-32C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR18	ENST00000585809.6	c.322-32C>A		intron_variant		1	NM_024100.4	P1

Frequencies

GnomAD3 genomes AF: 0.0886 AC: 13475 AN: 152082 Hom.: 771 Cov.: 32

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0690

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0791

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.0979

GnomAD3 exomes AF: 0.110 AC: 27376 AN: 248522 Hom.: 1874 AF XY: 0.119 AC XY: 16048 AN XY: 134768

Gnomad AFR exome AF: 0.0224

Gnomad AMR exome AF: 0.0538

Gnomad ASJ exome AF: 0.108

Gnomad EAS exome AF: 0.0802

Gnomad SAS exome AF: 0.196

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.120

Gnomad OTH exome AF: 0.122

GnomAD4 exome AF: 0.117 AC: 170680 AN: 1458866 Hom.: 10718 Cov.: 32 AF XY: 0.120 AC XY: 87162 AN XY: 725746

Gnomad4 AFR exome AF: 0.0237

Gnomad4 AMR exome AF: 0.0563

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.0759

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.0885 AC: 13473 AN: 152200 Hom.: 769 Cov.: 32 AF XY: 0.0909 AC XY: 6763 AN XY: 74406

Gnomad4 AFR AF: 0.0257

Gnomad4 AMR AF: 0.0689

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.0789

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.0969

Alfa AF: 0.118 Hom.: 1061

Bravo AF: 0.0784

Asia WGS AF: 0.151 AC: 524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.64
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2240147; hg19: chr19-989730; COSMIC: COSV52121942; COSMIC: COSV52121942;