rs369218093

Variant names:

• chr19-990233-G-A
• NM_024100.4:c.466G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-990233-G-A
• chr19-990233-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024100.4(WDR18):​c.466G>A​(p.Ala156Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,445,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A156S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: WDR18 NM_024100.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059639364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR18	NM_024100.4	c.466G>A	p.Ala156Thr	missense_variant	Exon 4 of 10	ENST00000585809.6	NP_077005.2
WDR18	NM_001372085.1	c.466G>A	p.Ala156Thr	missense_variant	Exon 6 of 12		NP_001359014.1
WDR18	NM_001372086.1	c.235G>A	p.Ala79Thr	missense_variant	Exon 7 of 13		NP_001359015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR18	ENST00000585809.6	c.466G>A	p.Ala156Thr	missense_variant	Exon 4 of 10	1	NM_024100.4	ENSP00000476117.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1445560 Hom.: 0 Cov.: 63 AF XY: 0.00000139 AC XY: 1 AN XY: 719602

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000256

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.0063	T;.
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.082	D
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.0	L;.
PrimateAI	Benign	0.27	T
Sift4G	Benign	0.27	T;T
Polyphen		0.049	B;.
Vest4		0.099
MutPred		0.33		Gain of phosphorylation at A156 (P = 0.1238);Gain of phosphorylation at A156 (P = 0.1238);
MVP		0.12
ClinPred		0.093	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.026
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-990233; COSMIC: COSV52120651; COSMIC: COSV52120651;