rs2240147

Variant names:

• chr19-989730-C-A
• rs2240147
• NM_024100.4:c.322-32C>A

Variant summary

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

The ENST00000585809.6(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 ENST00000585809.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234
• Publications: 23 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000585809.6. 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
	WDR18	NM_024100.4	MANE Select	c.322-32C>A		intron	N/A	NP_077005.2
	WDR18	NM_001372085.1		c.322-32C>A		intron	N/A	NP_001359014.1
	WDR18	NM_001372086.1		c.91-32C>A		intron	N/A	NP_001359015.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR18	ENST00000585809.6	TSL:1 MANE Select	c.322-32C>A		intron	N/A	ENSP00000476117.3
	WDR18	ENST00000251289.9	TSL:5	c.316-32C>A		intron	N/A	ENSP00000251289.4
	WDR18	ENST00000587001.6	TSL:5	c.322-32C>A		intron	N/A	ENSP00000464855.1

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

GnomAD2 exomes AF: 0.110 AC: 27376 AN: 248522 AF XY: 0.119

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 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

African (AFR) AF: 0.0237 AC: 793 AN: 33470

American (AMR) AF: 0.0563 AC: 2515 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 2739 AN: 26062

East Asian (EAS) AF: 0.0759 AC: 3012 AN: 39690

South Asian (SAS) AF: 0.195 AC: 16810 AN: 86212

European-Finnish (FIN) AF: 0.118 AC: 6022 AN: 51196

Middle Eastern (MID) AF: 0.135 AC: 775 AN: 5760

European-Non Finnish (NFE) AF: 0.118 AC: 130951 AN: 1111484

Other (OTH) AF: 0.117 AC: 7063 AN: 60342

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

African (AFR) AF: 0.0257 AC: 1067 AN: 41554

American (AMR) AF: 0.0689 AC: 1054 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 378 AN: 3466

East Asian (EAS) AF: 0.0789 AC: 407 AN: 5160

South Asian (SAS) AF: 0.200 AC: 963 AN: 4822

European-Finnish (FIN) AF: 0.124 AC: 1315 AN: 10618

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8018 AN: 67966

Other (OTH) AF: 0.0969 AC: 204 AN: 2106

Alfa AF: 0.111 Hom.: 1237

Bravo AF: 0.0784

Asia WGS AF: 0.151 AC: 524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.64
DANN	Benign	0.75
PhyloP100		0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2240147; hg19: chr19-989730; COSMIC: COSV52121942; COSMIC: COSV52121942;