Variant 16-685892-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032259.4(WDR24):c.1550C>T(p.Ser517Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,460,958 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: not found (cov: 34)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

WDR24
NM_032259.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.08

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28200585).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR24	NM_032259.4 linkuse as main transcript	c.1550C>T	p.Ser517Leu	missense_variant	5/9	ENST00000293883.9	NP_115635.1	Q96S15
WDR24	XM_047434767.1 linkuse as main transcript	c.1319C>T	p.Ser440Leu	missense_variant	5/9		XP_047290723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WDR24	ENST00000293883.9 linkuse as main transcript	c.1550C>T	p.Ser517Leu	missense_variant	5/9	1	NM_032259.4	ENSP00000293883.4	Q96S15
WDR24	ENST00000248142.7 linkuse as main transcript	c.1940C>T	p.Ser647Leu	missense_variant	9/13	5		ENSP00000248142.6	A0A499FJD3
WDR24	ENST00000647644.1 linkuse as main transcript	c.1772C>T	p.Ser591Leu	missense_variant	6/10			ENSP00000497264.1	A0A3B3ISA1
WDR24	ENST00000567014.1 linkuse as main transcript	n.481C>T		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1460958

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726774

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:

0.00000630

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 specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 17, 2022

The c.1550C>T (p.S517L) alteration is located in exon 5 (coding exon 5) of the WDR24 gene. This alteration results from a C to T substitution at nucleotide position 1550, causing the serine (S) at amino acid position 517 to be replaced by a leucine (L). 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

0.10

BayesDel_addAF

Uncertain

0.017

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.045

.;.;T

Eigen

Benign

-0.11

Eigen_PC

Benign

0.013

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Uncertain

0.085

MetaRNN

Benign

0.28

T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.69

.;.;N

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.4

N;.;N

REVEL

Benign

0.090

Sift

Benign

0.14

T;.;T

Sift4G

Benign

0.27

T;.;T

Polyphen

0.39

B;.;.

Vest4

0.48

MutPred

0.25

Gain of sheet (P = 0.0028);.;.;

MVP

0.82

MPC

0.44

ClinPred

0.72

GERP RS

4.7

Varity_R

0.13

gMVP

0.36

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

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