dbSNP rs13013415: WDR33:c.724+839A>G (chr2-127762223-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.682

Publications

8 publications found

Variant links:

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]

WDR33 links:

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ACMG classification

Classification was made for transcript

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

Sel.	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	Q9C0J8-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WDR33	ENST00000322313.9	TSL:1 MANE Select	c.724+839A>G	intron	N/A	ENSP00000325377.3	Q9C0J8-1
WDR33	ENST00000393006.5	TSL:1	c.724+839A>G	intron	N/A	ENSP00000376730.1	Q9C0J8-3
WDR33	ENST00000855799.1		c.724+839A>G	intron	N/A	ENSP00000525858.1

Frequencies

GnomAD3 genomes

AF:

0.0205

AC:

3115

AN:

152142

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0187

AC XY:

1396

AN XY:

74454

show subpopulations

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:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.0102

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00670

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0313

AC:

2127

AN:

68024

Other (OTH)

AF:

0.0317

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

153

305

458

610

763

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0246

Hom.:

Bravo

AF:

0.0217

Asia WGS

AF:

0.00693

AC:

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

(source)

DANN

Benign

0.65

PhyloP100

-0.68

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over