Variant X-49075636-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The ENST00000376372.9(WDR45):c.634C>A(p.Gln212Lys) 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. 14/20 in silico tools predict 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: 24)

Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

WDR45
ENST00000376372.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.43

Variant links:

Genes affected

WDR45 (HGNC:28912): (WD repeat domain 45) 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. This gene has a pseudogene at chromosome 4q31.3. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the biological validity and full-length nature of some variants have not been determined. [provided by RefSeq, Jul 2008]

WDR45 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a repeat WD 5 (size 39) in uniprot entity WIPI4_HUMAN there are 12 pathogenic changes around while only 2 benign (86%) in ENST00000376372.9

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26035154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR45	NM_001029896.2 linkuse as main transcript	c.634C>A	p.Gln212Lys	missense_variant	8/11	ENST00000376372.9	NP_001025067.1
WDR45	NM_007075.4 linkuse as main transcript	c.637C>A	p.Gln213Lys	missense_variant	9/12		NP_009006.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR45	ENST00000376372.9 linkuse as main transcript	c.634C>A	p.Gln212Lys	missense_variant	8/11	1	NM_001029896.2	ENSP00000365551	P4	Q9Y484-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

9.11e-7

AC:

AN:

1098178

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363534

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0071

T;T;.;T;T;.;T;.;.;.;T;.;T;.;T;T

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.86

D;.;D;D;D;T;D;D;.;T;T;D;T;D;D;D

M_CAP

Benign

0.033

MetaRNN

Benign

0.26

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.73

.;N;.;N;.;.;.;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

0.88

N;N;N;N;N;N;N;N

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.1

N;N;.;.;.;.;.;N;N;N;N;N;.;.;.;.

REVEL

Benign

0.073

Sift

Benign

0.090

T;T;.;.;.;.;.;T;T;T;T;T;.;.;.;.

Sift4G

Benign

0.75

T;T;T;T;T;T;T;T;T;T;T;T;T;.;.;.

Polyphen

0.041

B;B;.;B;.;.;.;B;B;B;B;B;.;.;.;.

Vest4

0.20

MutPred

0.40

.;Gain of ubiquitination at Q212 (P = 0.0128);.;Gain of ubiquitination at Q212 (P = 0.0128);.;Gain of ubiquitination at Q212 (P = 0.0128);.;.;.;.;Gain of ubiquitination at Q212 (P = 0.0128);.;.;.;.;.;

MVP

0.54

MPC

1.8

ClinPred

0.65

GERP RS

3.8

Varity_R

0.35

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over