Variant 16-684877-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032259.4(WDR24):c.2230G>A(p.Ala744Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000595 in 1,530,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000041 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000061 ( 0 hom. )

Consequence

WDR24
NM_032259.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.60

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:

Genome browser will be placed here

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=0.15213537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR24	NM_032259.4 link	c.2230G>A	p.Ala744Thr	missense_variant	9/9	ENST00000293883.9	NP_115635.1	Q96S15
WDR24	XM_047434767.1 link	c.1999G>A	p.Ala667Thr	missense_variant	9/9		XP_047290723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WDR24	ENST00000293883.9 link	c.2230G>A	p.Ala744Thr	missense_variant	9/9	1	NM_032259.4	ENSP00000293883.4	Q96S15
WDR24	ENST00000248142.7 link	c.2620G>A	p.Ala874Thr	missense_variant	13/13	5		ENSP00000248142.6	A0A499FJD3
WDR24	ENST00000647644.1 link	c.2452G>A	p.Ala818Thr	missense_variant	10/10			ENSP00000497264.1	A0A3B3ISA1

Frequencies

GnomAD3 genomes

AF:

0.0000407

AC:

AN:

147366

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00129

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000118

AC:

AN:

143768

Hom.:

AF XY:

0.000195

AC XY:

AN XY:

77068

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000752

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000615

AC:

AN:

1382650

Hom.:

Cov.:

AF XY:

0.0000911

AC XY:

AN XY:

680868

show subpopulations

Gnomad4 AFR exome

AF:

0.0000639

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000949

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000187

Gnomad4 OTH exome

AF:

0.000105

GnomAD4 genome

AF:

0.0000407

AC:

AN:

147366

Hom.:

Cov.:

AF XY:

0.0000700

AC XY:

AN XY:

71460

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00129

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000894

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2024

The c.2230G>A (p.A744T) alteration is located in exon 9 (coding exon 9) of the WDR24 gene. This alteration results from a G to A substitution at nucleotide position 2230, causing the alanine (A) at amino acid position 744 to be replaced by a threonine (T). 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

0.47

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

.;.;T

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.44

MutationAssessor

Benign

1.8

.;.;L

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.53

N;.;N

REVEL

Benign

0.28

Sift

Benign

0.18

T;.;T

Sift4G

Benign

0.068

T;.;T

Polyphen

0.94

P;.;.

Vest4

0.69

MutPred

0.48

Gain of sheet (P = 0.0827);.;.;

MVP

0.83

MPC

1.0

ClinPred

0.19

GERP RS

4.8

Varity_R

0.18

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over