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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR18	NM_024100.4 link	c.199C>T	p.Leu67Phe	missense_variant	Exon 1 of 10	ENST00000585809.6	NP_077005.2	Q9BV38
WDR18	NM_001372085.1 link	c.199C>T	p.Leu67Phe	missense_variant	Exon 3 of 12		NP_001359014.1
WDR18	NM_001372086.1 link	c.-33C>T		5_prime_UTR_variant	Exon 4 of 13		NP_001359015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR18	ENST00000585809.6 link	c.199C>T	p.Leu67Phe	missense_variant	Exon 1 of 10	1	NM_024100.4	ENSP00000476117.3		Q9BV38

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

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.199C>T (p.L67F) alteration is located in exon 1 (coding exon 1) of the WDR18 gene. This alteration results from a C to T substitution at nucleotide position 199, causing the leucine (L) at amino acid position 67 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;.;.

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.21

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.067

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.;.

PrimateAI

Uncertain

0.62

Sift4G

Uncertain

0.018

D;D;D

Polyphen

0.99

D;.;.

Vest4

0.40

MutPred

0.33

Gain of methylation at K70 (P = 0.0805);Gain of methylation at K70 (P = 0.0805);.;

MVP

0.093

ClinPred

0.90

GERP RS

2.0

Varity_R

0.25

gMVP

0.45

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over