rs2042415

Positions:

• chr16-74944720-G-A
• chr16-74944720-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030581.4(WDR59):​c.446-1894C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0705 in 151,996 control chromosomes in the GnomAD database, including 710 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.070 (710 hom., cov: 31)
• Consequence: WDR59 NM_030581.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550

Genes affected

WDR59 (HGNC:25706): (WD repeat domain 59) Involved in cellular response to amino acid starvation and positive regulation of TOR signaling. Located in lysosomal membrane. Part of GATOR2 complex. [provided by Alliance of Genome Resources, Apr 2022]

WDR59 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR59	NM_030581.4	c.446-1894C>T		intron_variant		ENST00000262144.11	NP_085058.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR59	ENST00000262144.11	c.446-1894C>T		intron_variant		5	NM_030581.4	ENSP00000262144.6

Frequencies

GnomAD3 genomes AF: 0.0705 AC: 10711 AN: 151878 Hom.: 710 Cov.: 31

Gnomad AFR AF: 0.0166

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0620

Gnomad OTH AF: 0.0720

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

GnomAD4 genome AF: 0.0705 AC: 10714 AN: 151996 Hom.: 710 Cov.: 31 AF XY: 0.0772 AC XY: 5735 AN XY: 74280

Gnomad4 AFR AF: 0.0165

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.0392

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.0620

Gnomad4 OTH AF: 0.0764

Alfa AF: 0.0667 Hom.: 540

Bravo AF: 0.0689

Asia WGS AF: 0.234 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.57

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: rs2042415; hg19: chr16-74978618;