Variant chr16-685448-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.1828G>A(p.Val610Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,455,536 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 1 hom. )

Consequence

WDR24
NM_032259.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07008195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR24	NM_032259.4 linkuse as main transcript	c.1828G>A	p.Val610Met	missense_variant	7/9	ENST00000293883.9
WDR24	XM_047434767.1 linkuse as main transcript	c.1597G>A	p.Val533Met	missense_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
WDR24	ENST00000293883.9 linkuse as main transcript	c.1828G>A	p.Val610Met	missense_variant	7/9	1	NM_032259.4	P1
WDR24	ENST00000248142.7 linkuse as main transcript	c.2218G>A	p.Val740Met	missense_variant	11/13	5
WDR24	ENST00000647644.1 linkuse as main transcript	c.2050G>A	p.Val684Met	missense_variant	8/10
WDR24	ENST00000567014.1 linkuse as main transcript			downstream_gene_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1455536

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723026

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.03e-7

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 05, 2024

The c.1828G>A (p.V610M) alteration is located in exon 7 (coding exon 7) of the WDR24 gene. This alteration results from a G to A substitution at nucleotide position 1828, causing the valine (V) at amino acid position 610 to be replaced by a methionine (M). 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

0.086

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0071

.;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.070

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.1

.;.;L

MutationTaster

Benign

1.0

D;D;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.32

N;.;N

REVEL

Benign

0.12

Sift

Benign

0.10

T;.;T

Sift4G

Benign

0.13

T;.;T

Polyphen

0.0010

B;.;.

Vest4

0.35

MutPred

0.17

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

MVP

0.61

MPC

0.41

ClinPred

0.082

GERP RS

-0.23

Varity_R

0.032

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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