16-684894-C-A

Position:

• chr16-684894-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032259.4(WDR24):​c.2213G>T​(p.Arg738Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000361 in 276,882 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: 29)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: WDR24 NM_032259.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.69

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]

ACMG classification

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=0.30569333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR24	NM_032259.4	c.2213G>T	p.Arg738Leu	missense_variant	9/9	ENST00000293883.9	NP_115635.1
WDR24	XM_047434767.1	c.1982G>T	p.Arg661Leu	missense_variant	9/9		XP_047290723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR24	ENST00000293883.9	c.2213G>T	p.Arg738Leu	missense_variant	9/9	1	NM_032259.4	ENSP00000293883.4
WDR24	ENST00000248142.7	c.2603G>T	p.Arg868Leu	missense_variant	13/13	5		ENSP00000248142.6
WDR24	ENST00000647644.1	c.2435G>T	p.Arg812Leu	missense_variant	10/10			ENSP00000497264.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000361 AC: 1 AN: 276882 Hom.: 0 Cov.: 0 AF XY: 0.00000668 AC XY: 1 AN XY: 149636

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: 0.0000192

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.2213G>T (p.R738L) alteration is located in exon 9 (coding exon 9) of the WDR24 gene. This alteration results from a G to T substitution at nucleotide position 2213, causing the arginine (R) at amino acid position 738 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	0.18
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.064	.;.;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.6	.;.;L
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.5	N;.;N
REVEL	Benign	0.18
Sift	Benign	0.077	T;.;T
Sift4G	Uncertain	0.045	D;.;T
Polyphen		0.15	B;.;.
Vest4		0.36
MutPred		0.55		Loss of solvent accessibility (P = 0.0052);.;.;
MVP		0.79
MPC		0.58
ClinPred		0.70	D
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.48

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

Other links and lift over

dbSNP: rs1232722096; hg19: chr16-734894;