16-684798-A-G

Position:

• chr16-684798-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032259.4(WDR24):​c.2309T>C​(p.Met770Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,438,590 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: WDR24 NM_032259.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.81

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR24	NM_032259.4	c.2309T>C	p.Met770Thr	missense_variant	9/9	ENST00000293883.9	NP_115635.1
WDR24	XM_047434767.1	c.2078T>C	p.Met693Thr	missense_variant	9/9		XP_047290723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR24	ENST00000293883.9	c.2309T>C	p.Met770Thr	missense_variant	9/9	1	NM_032259.4	ENSP00000293883.4
WDR24	ENST00000248142.7	c.2699T>C	p.Met900Thr	missense_variant	13/13	5		ENSP00000248142.6
WDR24	ENST00000647644.1	c.2531T>C	p.Met844Thr	missense_variant	10/10			ENSP00000497264.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1438590 Hom.: 0 Cov.: 33 AF XY: 0.00000280 AC XY: 2 AN XY: 714014

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: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Aug 10, 2024

The c.2309T>C (p.M770T) alteration is located in exon 9 (coding exon 9) of the WDR24 gene. This alteration results from a T to C substitution at nucleotide position 2309, causing the methionine (M) at amino acid position 770 to be replaced by a threonine (T). 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	0.34
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Benign	0.56
DEOGEN2	Benign	0.016	.;.;T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.054
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.51	D;D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.1	.;.;L
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.060	N;.;N
REVEL	Benign	0.24
Sift	Benign	0.51	T;.;T
Sift4G	Benign	0.52	T;.;T
Polyphen		0.065	B;.;.
Vest4		0.64
MutPred		0.54		Gain of methylation at K771 (P = 0.0311);.;.;
MVP		0.80
MPC		0.48
ClinPred		0.94	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr16-734798;