rs13013415

Positions:

• chr2-127762223-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 64 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR33	NM_018383.5	c.724+839A>G		intron_variant		ENST00000322313.9	NP_060853.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR33	ENST00000322313.9	c.724+839A>G		intron_variant		1	NM_018383.5	ENSP00000325377	P1
WDR33	ENST00000393006.5	c.724+839A>G		intron_variant		1		ENSP00000376730
WDR33	ENST00000436787.5	c.490+839A>G		intron_variant		5		ENSP00000397547

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

Gnomad4 AFR AF: 0.00525

Gnomad4 AMR AF: 0.0334

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0102

Gnomad4 FIN AF: 0.00670

Gnomad4 NFE AF: 0.0313

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0264 Hom.: 47

Bravo AF: 0.0217

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.62
DANN	Benign	0.65

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: rs13013415; hg19: chr2-128519797;