rs17015535

Variant names:

• chr2-127745011-A-T
• rs17015535
• NM_018383.5:c.724+18051T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018383.5(WDR33):​c.724+18051T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.027 in 152,184 control chromosomes in the GnomAD database, including 200 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 0.027 (200 hom., cov: 32)
• Consequence: WDR33 NM_018383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 5 publications found

Genes affected

WDR33 (HGNC:25651): (WD repeat domain 33) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene is highly expressed in testis and the protein is localized to the nucleus. This gene may play important roles in the mechanisms of cytodifferentiation and/or DNA recombination. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR33	NM_018383.5	c.724+18051T>A		intron_variant	Intron 7 of 21	ENST00000322313.9	NP_060853.3
WDR33	NM_001006623.4	c.725-6957T>A		intron_variant	Intron 7 of 7		NP_001006624.1
WDR33	XM_011511436.2	c.724+18051T>A		intron_variant	Intron 7 of 21		XP_011509738.1
WDR33	XM_005263697.4	c.724+18051T>A		intron_variant	Intron 7 of 20		XP_005263754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR33	ENST00000322313.9	c.724+18051T>A		intron_variant	Intron 7 of 21	1	NM_018383.5	ENSP00000325377.3
WDR33	ENST00000393006.5	c.725-6957T>A		intron_variant	Intron 7 of 7	1		ENSP00000376730.1
WDR33	ENST00000436787.5	c.490+18051T>A		intron_variant	Intron 6 of 6	5		ENSP00000397547.1

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 4097 AN: 152066 Hom.: 199 Cov.: 32

Gnomad AFR AF: 0.0930

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0121

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0239

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

GnomAD4 genome AF: 0.0270 AC: 4110 AN: 152184 Hom.: 200 Cov.: 32 AF XY: 0.0265 AC XY: 1974 AN XY: 74406

African (AFR) AF: 0.0930 AC: 3860 AN: 41504

American (AMR) AF: 0.0120 AC: 184 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68008

Other (OTH) AF: 0.0236 AC: 50 AN: 2116

Alfa AF: 0.0209 Hom.: 16

Bravo AF: 0.0314

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	15
DANN	Benign	0.83
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17015535; hg19: chr2-128502585;