Variant 16-685459-G-A 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.1817C>T(p.Ser606Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 1,605,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

WDR24
NM_032259.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.80

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=0.15138802).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR24	NM_032259.4 link	c.1817C>T	p.Ser606Phe	missense_variant	7/9	ENST00000293883.9	NP_115635.1	Q96S15
WDR24	XM_047434767.1 link	c.1586C>T	p.Ser529Phe	missense_variant	7/9		XP_047290723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WDR24	ENST00000293883.9 link	c.1817C>T	p.Ser606Phe	missense_variant	7/9	1	NM_032259.4	ENSP00000293883.4	Q96S15
WDR24	ENST00000248142.7 link	c.2207C>T	p.Ser736Phe	missense_variant	11/13	5		ENSP00000248142.6	A0A499FJD3
WDR24	ENST00000647644.1 link	c.2039C>T	p.Ser680Phe	missense_variant	8/10			ENSP00000497264.1	A0A3B3ISA1
WDR24	ENST00000567014.1 link	n.748C>T		non_coding_transcript_exon_variant	4/4	5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000407

AC:

AN:

245934

Hom.:

AF XY:

0.00000747

AC XY:

AN XY:

133864

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

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:

0.0000117

AC:

AN:

1453156

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

721242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000269

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000723

Gnomad4 OTH exome

AF:

0.0000334

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

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

Sep 23, 2023

The c.1817C>T (p.S606F) alteration is located in exon 7 (coding exon 7) of the WDR24 gene. This alteration results from a C to T substitution at nucleotide position 1817, causing the serine (S) at amino acid position 606 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

Benign

0.18

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.26

.;.;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.80

T;T;T

M_CAP

Uncertain

0.087

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.9

.;.;L

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.5

D;.;D

REVEL

Benign

0.17

Sift

Uncertain

0.0060

D;.;D

Sift4G

Uncertain

0.020

D;.;D

Polyphen

0.0

B;.;.

Vest4

0.47

MutPred

0.31

Loss of disorder (P = 0.011);.;.;

MVP

0.78

MPC

0.45

ClinPred

0.28

GERP RS

3.8

Varity_R

0.19

gMVP

0.45

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