16-685729-ACG-A

Position:

• chr16-685729-ACG-A

Variant summary

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

The NM_032259.4(WDR24):​c.1626_1627delCG​(p.Val543fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDR24 NM_032259.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.34

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.1626_1627delCG	p.Val543fs	frameshift_variant	6/9	ENST00000293883.9	NP_115635.1
WDR24	XM_047434767.1	c.1395_1396delCG	p.Val466fs	frameshift_variant	6/9		XP_047290723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR24	ENST00000293883.9	c.1626_1627delCG	p.Val543fs	frameshift_variant	6/9	1	NM_032259.4	ENSP00000293883.4
WDR24	ENST00000248142.7	c.2016_2017delCG	p.Val673fs	frameshift_variant	10/13	5		ENSP00000248142.6
WDR24	ENST00000647644.1	c.1848_1849delCG	p.Val617fs	frameshift_variant	7/10			ENSP00000497264.1
WDR24	ENST00000567014.1	n.557_558delCG		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Clinical Genomics Laboratory, Washington University in St. Louis

Sep 05, 2023

The WDR24 c.1626_1627del (p.Val543GlyfsTer3) variant, to our knowledge, has not been reported in the medical literature and is absent from the general population (gnomAD v.2.1.1), indicating it is not a common variant. This variant causes a frameshift by deleting two nucleotides, leading to a premature termination codon, which is predicted to lead to nonsense mediated decay. Due to limited information, the clinical significance of this variant is uncertain. -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: chr16-735729;