NM_024100.4:c.369C>T

Variant names:

• chr19-989809-C-T
• rs760596218
• NM_024100.4:c.369C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_024100.4(WDR18):​c.369C>T​(p.Asp123Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,530 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: WDR18 NM_024100.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• Publications: 1 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=-0.067 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024100.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR18	NM_024100.4	MANE Select	c.369C>T	p.Asp123Asp	synonymous	Exon 3 of 10	NP_077005.2	Q9BV38
	WDR18	NM_001372085.1		c.369C>T	p.Asp123Asp	synonymous	Exon 5 of 12	NP_001359014.1	Q9BV38
	WDR18	NM_001372086.1		c.138C>T	p.Asp46Asp	synonymous	Exon 6 of 13	NP_001359015.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR18	ENST00000585809.6	TSL:1 MANE Select	c.369C>T	p.Asp123Asp	synonymous	Exon 3 of 10	ENSP00000476117.3	Q9BV38
	WDR18	ENST00000886865.1		c.304C>T	p.Arg102Cys	missense	Exon 3 of 10	ENSP00000556924.1
	WDR18	ENST00000886864.1		c.369C>T	p.Asp123Asp	synonymous	Exon 3 of 10	ENSP00000556923.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000798 AC: 2 AN: 250530 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1460530 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 726588

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111854

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.2
DANN	Benign	0.57
PhyloP100		-0.067
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs760596218; hg19: chr19-989809; COSMIC: COSV99243156; COSMIC: COSV99243156;