X-48601844-G-T

Position:

chrX-48601844-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP6BS2

The NM_001347217.2(WDR13):c.892G>T(p.Gly298Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000973 in 1,202,565 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 47 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000089 ( 0 hom., 3 hem., cov: 24)

Exomes 𝑓: 0.000098 ( 0 hom. 44 hem. )

Consequence

WDR13
NM_001347217.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:1

Conservation

PhyloP100: 8.64

Variant links:

Genes affected

WDR13 (HGNC:14352): (WD repeat domain 13) 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. A similar protein in mouse is thought to be a negative regulator of the pancreatic beta cell proliferation. Mice lacking this gene exhibit increased pancreatic islet mass and higher serum insulin levels, and are mildly obese. [provided by RefSeq, Nov 2016]

WDR13 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), WDR13. . Gene score misZ 3.2948 (greater than the threshold 3.09). GenCC has associacion of gene with intellectual disability.

BP6

Variant X-48601844-G-T is Benign according to our data. Variant chrX-48601844-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1206159.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR13	NM_001347217.2 linkuse as main transcript	c.892G>T	p.Gly298Trp	missense_variant	7/10	ENST00000376729.10	NP_001334146.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
WDR13	ENST00000376729.10 linkuse as main transcript	c.892G>T	p.Gly298Trp	missense_variant	7/10	5	NM_001347217.2	ENSP00000365919	P1
WDR13	ENST00000218056.9 linkuse as main transcript	c.892G>T	p.Gly298Trp	missense_variant	6/9	1		ENSP00000218056	P1
WDR13	ENST00000479279.5 linkuse as main transcript	n.1759G>T		non_coding_transcript_exon_variant	5/8	1
WDR13	ENST00000482760.3 linkuse as main transcript	c.136G>T	p.Gly46Trp	missense_variant	2/5	3		ENSP00000483191

Frequencies

GnomAD3 genomes

AF:

0.0000887

AC:

AN:

112735

Hom.:

Cov.:

AF XY:

0.0000860

AC XY:

AN XY:

34887

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000187

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:

0.000150

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000116

AC:

AN:

172041

Hom.:

AF XY:

0.000138

AC XY:

AN XY:

57995

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000389

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000179

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000208

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000982

AC:

107

AN:

1089830

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

356856

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000585

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000265

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000955

Gnomad4 OTH exome

AF:

0.000109

GnomAD4 genome

AF:

0.0000887

AC:

AN:

112735

Hom.:

Cov.:

AF XY:

0.0000860

AC XY:

AN XY:

34887

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000187

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000150

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000220

Hom.:

Bravo

AF:

0.0000869

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.000214

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:2Benign:1

Uncertain significance, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	WDR13: PP2, BS2 -
Uncertain significance, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 20, 2023

The c.892G>T (p.G298W) alteration is located in exon 6 (coding exon 6) of the WDR13 gene. This alteration results from a G to T substitution at nucleotide position 892, causing the glycine (G) at amino acid position 298 to be replaced by a tryptophan (W). 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

Pathogenic

0.90

BayesDel_addAF

Uncertain

0.085

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

.;.;T

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

.;.;D

M_CAP

Uncertain

0.25

MetaRNN

Uncertain

0.49

T;T;T

MetaSVM

Benign

-0.46

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-4.9

D;D;.

REVEL

Uncertain

0.52

Sift

Pathogenic

0.0

D;D;.

Sift4G

Pathogenic

0.0

D;D;D

Vest4

0.21

MVP

0.81

MPC

2.4

ClinPred

0.22

GERP RS

5.4

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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