Variant 15-89701885-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020212.2(WDR93):c.139G>C(p.Asp47His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000287 in 1,614,086 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 1 hom. )

Consequence

WDR93
NM_020212.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.92

Variant links:

Genes affected

WDR93 (HGNC:26924): (WD repeat domain 93) Predicted to enable oxidoreductase activity, acting on NAD(P)H. Predicted to be involved in electron transport chain. Predicted to be part of mitochondrial respiratory chain complex I. [provided by Alliance of Genome Resources, Apr 2022]

WDR93 links:

WDR93 (HGNC:):

WDR93 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.048947424).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR93	NM_020212.2 linkuse as main transcript	c.139G>C	p.Asp47His	missense_variant	2/17	ENST00000268130.12	NP_064597.1	Q6P2C0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WDR93	ENST00000268130.12 linkuse as main transcript	c.139G>C	p.Asp47His	missense_variant	2/17	1	NM_020212.2	ENSP00000268130.7	Q6P2C0-1
WDR93	ENST00000558000.1 linkuse as main transcript	c.139G>C	p.Asp47His	missense_variant	2/3	1		ENSP00000453022.1	B4E3E2
WDR93	ENST00000560294.5 linkuse as main transcript	c.139G>C	p.Asp47His	missense_variant	2/17	2		ENSP00000453971.1	Q6P2C0-2

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000470

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000239

AC:

AN:

251128

Hom.:

AF XY:

0.000265

AC XY:

AN XY:

135708

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000485

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000291

AC:

425

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000289

AC XY:

210

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000371

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000250

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000470

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000491

Hom.:

Bravo

AF:

0.000234

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000222

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000948

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

Mar 15, 2024

The c.139G>C (p.D47H) alteration is located in exon 2 (coding exon 1) of the WDR93 gene. This alteration results from a G to C substitution at nucleotide position 139, causing the aspartic acid (D) at amino acid position 47 to be replaced by a histidine (H). 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

Benign

0.14

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.025

T;.;T

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.38

T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.049

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;L;.

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-3.5

D;D;D

REVEL

Benign

0.032

Sift

Uncertain

0.019

D;D;D

Sift4G

Uncertain

0.015

D;D;D

Polyphen

0.21

B;P;B

Vest4

0.23

MVP

0.067

MPC

0.11

ClinPred

0.068

GERP RS

2.6

Varity_R

0.077

gMVP

0.32

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

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