Variant chr2-189441515-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032168.3(WDR75):c.23G>T(p.Arg8Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000212 in 1,414,190 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

WDR75
NM_032168.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.77

Variant links:

Genes affected

WDR75 (HGNC:25725): (WD repeat domain 75) Enables RNA binding activity. Involved in positive regulation of rRNA processing and positive regulation of transcription by RNA polymerase I. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

WDR75 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR75	NM_032168.3 linkuse as main transcript	c.23G>T	p.Arg8Leu	missense_variant	1/21	ENST00000314761.9	NP_115544.1
WDR75	NM_001303096.2 linkuse as main transcript	c.-204G>T		5_prime_UTR_variant	1/22		NP_001290025.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR75	ENST00000314761.9 linkuse as main transcript	c.23G>T	p.Arg8Leu	missense_variant	1/21	1	NM_032168.3	ENSP00000314193	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000111

AC:

AN:

179670

Hom.:

AF XY:

0.0000210

AC XY:

AN XY:

95166

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000412

GnomAD4 exome

AF:

0.00000212

AC:

AN:

1414190

Hom.:

Cov.:

AF XY:

0.00000429

AC XY:

AN XY:

698680

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.21e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000846

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 12, 2023

The c.23G>T (p.R8L) alteration is located in exon 1 (coding exon 1) of the WDR75 gene. This alteration results from a G to T substitution at nucleotide position 23, causing the arginine (R) at amino acid position 8 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.20

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.092

T;.

Eigen

Pathogenic

0.68

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.82

T;T

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.44

T;T

MetaSVM

Benign

-0.34

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.9

N;.

REVEL

Uncertain

0.41

Sift

Benign

0.30

T;.

Sift4G

Uncertain

0.016

D;D

Polyphen

1.0

D;.

Vest4

0.51

MutPred

0.54

Loss of disorder (P = 0.0513);Loss of disorder (P = 0.0513);

MVP

0.52

MPC

0.26

ClinPred

0.93

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.41

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over