rs13013415

Variant names:

• chr2-127762223-T-C
• rs13013415
• NM_018383.5:c.724+839A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_018383.5(WDR33):​c.724+839A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0205 in 152,260 control chromosomes in the GnomAD database, including 64 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 0.020 (64 hom., cov: 32)
• Consequence: WDR33 NM_018383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.682
• Publications: 8 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=-0.86).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0205 (3114/152260) while in subpopulation AMR AF = 0.0334 (510/15288). AF 95% confidence interval is 0.031. There are 64 homozygotes in GnomAd4. There are 1396 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 64 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018383.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR33	NM_018383.5	MANE Select	c.724+839A>G		intron	N/A	NP_060853.3
	WDR33	NM_001006623.4		c.724+839A>G		intron	N/A	NP_001006624.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR33	ENST00000322313.9	TSL:1 MANE Select	c.724+839A>G		intron	N/A	ENSP00000325377.3
	WDR33	ENST00000393006.5	TSL:1	c.724+839A>G		intron	N/A	ENSP00000376730.1
	WDR33	ENST00000436787.5	TSL:5	c.490+839A>G		intron	N/A	ENSP00000397547.1

Frequencies

GnomAD3 genomes AF: 0.0205 AC: 3115 AN: 152142 Hom.: 64 Cov.: 32

Gnomad AFR AF: 0.00524

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0334

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0101

Gnomad FIN AF: 0.00670

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0313

Gnomad OTH AF: 0.0320

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

GnomAD4 genome AF: 0.0205 AC: 3114 AN: 152260 Hom.: 64 Cov.: 32 AF XY: 0.0187 AC XY: 1396 AN XY: 74454

African (AFR) AF: 0.00525 AC: 218 AN: 41550

American (AMR) AF: 0.0334 AC: 510 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.0102 AC: 49 AN: 4826

European-Finnish (FIN) AF: 0.00670 AC: 71 AN: 10602

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0313 AC: 2127 AN: 68024

Other (OTH) AF: 0.0317 AC: 67 AN: 2116

Alfa AF: 0.0246 Hom.: 70

Bravo AF: 0.0217

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.62
DANN	Benign	0.65
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism

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: rs13013415; hg19: chr2-128519797;