Variant chr16-686186-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032259.4(WDR24):c.1333G>A(p.Val445Met) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000123 in 1,460,124 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

WDR24
NM_032259.4 missense, splice_region

Scores

Splicing: ADA: 0.9999

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.97

Variant links:

Genes affected

WDR24 (HGNC:20852): (WD repeat domain 24) Involved in cellular response to amino acid starvation; positive regulation of TOR signaling; and regulation of autophagy. Located in cytosol and lysosomal membrane. Part of GATOR2 complex. [provided by Alliance of Genome Resources, Apr 2022]

WDR24 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR24	NM_032259.4 linkuse as main transcript	c.1333G>A	p.Val445Met	missense_variant, splice_region_variant	4/9	ENST00000293883.9
WDR24	XM_047434767.1 linkuse as main transcript	c.1102G>A	p.Val368Met	missense_variant, splice_region_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
WDR24	ENST00000293883.9 linkuse as main transcript	c.1333G>A	p.Val445Met	missense_variant, splice_region_variant	4/9	1	NM_032259.4	P1
WDR24	ENST00000248142.7 linkuse as main transcript	c.1723G>A	p.Val575Met	missense_variant, splice_region_variant	8/13	5
WDR24	ENST00000647644.1 linkuse as main transcript	c.1555G>A	p.Val519Met	missense_variant, splice_region_variant	5/10
WDR24	ENST00000567014.1 linkuse as main transcript	n.187G>A		splice_region_variant, non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1460124

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726370

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

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 provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Clinical Genomics Laboratory, Washington University in St. Louis

Sep 05, 2023

The WDR24 c.1333G>A (p.Val445Met) variant, to our knowledge, has not been reported in the medical literature and is absent from the general population (gnomAD v.2.1.1), indicating it is not a common variant. This variant is in an alpha helical domain and computational predictors indicate that the variant is damaging, evidence that correlates with impact to WDR24 function. Due to limited information, the clinical significance of this variant is uncertain. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.064

.;.;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.062

MetaRNN

Uncertain

0.58

D;D;D

MetaSVM

Uncertain

-0.11

MutationAssessor

Uncertain

2.4

.;.;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.7

N;.;N

REVEL

Uncertain

0.35

Sift

Uncertain

0.011

D;.;D

Sift4G

Uncertain

0.037

D;.;D

Polyphen

0.90

P;.;.

Vest4

0.83

MutPred

0.36

Gain of sheet (P = 0.039);.;.;

MVP

0.83

MPC

1.1

ClinPred

0.95

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.97

SpliceAI score (max)

0.080

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