Genetic Variant WDR18:p.Leu67Phe (chr19-984552-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024100.4(WDR18):c.199C>T(p.Leu67Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

WDR18
NM_024100.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.52

Publications

0 publications found

Variant links:

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]

WDR18 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24982244).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDR18	NM_024100.4	MANE Select	c.199C>T	p.Leu67Phe	missense	Exon 1 of 10	NP_077005.2	Q9BV38
WDR18	NM_001372085.1		c.199C>T	p.Leu67Phe	missense	Exon 3 of 12	NP_001359014.1	Q9BV38
WDR18	NM_001372086.1		c.-33C>T		5_prime_UTR	Exon 4 of 13	NP_001359015.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDR18	ENST00000585809.6	TSL:1 MANE Select	c.199C>T	p.Leu67Phe	missense	Exon 1 of 10	ENSP00000476117.3	Q9BV38
WDR18	ENST00000886864.1		c.199C>T	p.Leu67Phe	missense	Exon 1 of 10	ENSP00000556923.1
WDR18	ENST00000933666.1		c.199C>T	p.Leu67Phe	missense	Exon 1 of 11	ENSP00000603725.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1346770

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

661356

African (AFR)

AF:

0.00

AC:

AN:

28060

American (AMR)

AF:

0.00

AC:

AN:

30180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23248

East Asian (EAS)

AF:

0.00

AC:

AN:

31320

South Asian (SAS)

AF:

0.00

AC:

AN:

73466

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44166

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5418

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1054922

Other (OTH)

AF:

0.00

AC:

AN:

55990

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.21

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.067

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

1.5

PrimateAI

Uncertain

0.62

Sift4G

Uncertain

0.018

Polyphen

0.99

Vest4

0.40

MutPred

0.33

Gain of methylation at K70 (P = 0.0805)

MVP

0.093

ClinPred

0.90

GERP RS

2.0

PromoterAI

0.048

Neutral

(source)

Varity_R

0.25

gMVP

0.45

Mutation Taster

=70/30

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over