16-685480-C-T

Position:

• chr16-685480-C-T

Variant summary

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

The NM_032259.4(WDR24):​c.1796G>A​(p.Gly599Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: WDR24 NM_032259.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.52

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=0.3624701).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR24	NM_032259.4	c.1796G>A	p.Gly599Asp	missense_variant	7/9	ENST00000293883.9
WDR24	XM_047434767.1	c.1565G>A	p.Gly522Asp	missense_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR24	ENST00000293883.9	c.1796G>A	p.Gly599Asp	missense_variant	7/9	1	NM_032259.4	P1
WDR24	ENST00000248142.7	c.2186G>A	p.Gly729Asp	missense_variant	11/13	5
WDR24	ENST00000647644.1	c.2018G>A	p.Gly673Asp	missense_variant	8/10
WDR24	ENST00000567014.1	n.727G>A		non_coding_transcript_exon_variant	4/4	5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 34

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

Feb 23, 2023

The c.1796G>A (p.G599D) 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 1796, causing the glycine (G) at amino acid position 599 to be replaced by an aspartic acid (D). 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	0.44
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0029	.;.;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Uncertain	0.096	D
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.3	.;.;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.37	N;.;N
REVEL	Uncertain	0.30
Sift	Benign	0.50	T;.;T
Sift4G	Benign	0.68	T;.;T
Polyphen		1.0	D;.;.
Vest4		0.92
MutPred		0.19		Loss of glycosylation at S598 (P = 0.0323);.;.;
MVP		0.82
MPC		1.4
ClinPred		0.90	D
GERP RS		4.7
Varity_R		0.23
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr16-735480;