Variant 16-685426-A-G 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.1850T>C(p.Leu617Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000807 in 1,611,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

WDR24
NM_032259.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.87

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:

WDR24 (HGNC:):

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=0.1265971).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR24	NM_032259.4 linkuse as main transcript	c.1850T>C	p.Leu617Pro	missense_variant	7/9	ENST00000293883.9	NP_115635.1	Q96S15
WDR24	XM_047434767.1 linkuse as main transcript	c.1619T>C	p.Leu540Pro	missense_variant	7/9		XP_047290723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WDR24	ENST00000293883.9 linkuse as main transcript	c.1850T>C	p.Leu617Pro	missense_variant	7/9	1	NM_032259.4	ENSP00000293883.4	Q96S15
WDR24	ENST00000248142.7 linkuse as main transcript	c.2240T>C	p.Leu747Pro	missense_variant	11/13	5		ENSP00000248142.6	A0A499FJD3
WDR24	ENST00000647644.1 linkuse as main transcript	c.2072T>C	p.Leu691Pro	missense_variant	8/10			ENSP00000497264.1	A0A3B3ISA1
WDR24	ENST00000567014.1 linkuse as main transcript	n.*24T>C		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152232

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:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000444

AC:

AN:

247624

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

134640

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000610

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000822

AC:

AN:

1459272

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725710

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152350

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000578

AC:

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

Mar 28, 2024

The c.1850T>C (p.L617P) alteration is located in exon 7 (coding exon 7) of the WDR24 gene. This alteration results from a T to C substitution at nucleotide position 1850, causing the leucine (L) at amino acid position 617 to be replaced by a proline (P). 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

0.41

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

.;.;T

Eigen

Benign

-0.059

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

1.3

.;.;L

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.3

N;.;N

REVEL

Uncertain

0.37

Sift

Uncertain

0.0020

D;.;D

Sift4G

Uncertain

0.0070

D;.;D

Polyphen

0.12

B;.;.

Vest4

0.54

MutPred

0.53

Gain of loop (P = 0.0045);.;.;

MVP

0.86

MPC

0.66

ClinPred

0.28

GERP RS

4.8

Varity_R

0.64

gMVP

0.80

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