rs17730281

Positions:

chr15-53615751-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182758.4(WDR72):c.2455C>T(p.Leu819Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,613,084 control chromosomes in the GnomAD database, including 46,614 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4079 hom., cov: 32)

Exomes 𝑓: 0.23 ( 42535 hom. )

Consequence

WDR72
NM_182758.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.07

Variant links:

Genes affected

WDR72 (HGNC:26790): (WD repeat domain 72) This gene encodes a protein with eight WD-40 repeats. Mutations in this gene have been associated with amelogenesis imperfecta hypomaturation type 2A3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

WDR72 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003987491).

BP6

Variant 15-53615751-G-A is Benign according to our data. Variant chr15-53615751-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 262999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-53615751-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR72	NM_182758.4 linkuse as main transcript	c.2455C>T	p.Leu819Phe	missense_variant	15/20	ENST00000360509.10	NP_877435.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
WDR72	ENST00000360509.10 linkuse as main transcript	c.2455C>T	p.Leu819Phe	missense_variant	15/20	1	NM_182758.4	ENSP00000353699	P4
WDR72	ENST00000396328.5 linkuse as main transcript	c.2455C>T	p.Leu819Phe	missense_variant	15/20	1		ENSP00000379619	P4
WDR72	ENST00000559418.5 linkuse as main transcript	c.2485C>T	p.Leu829Phe	missense_variant	14/19	5		ENSP00000452765
WDR72	ENST00000557913.5 linkuse as main transcript	c.2446C>T	p.Leu816Phe	missense_variant	15/20	5		ENSP00000453378	A1

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33384

AN:

151756

Hom.:

4066

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.161

Gnomad AMR

AF:

0.307

Gnomad ASJ

AF:

0.0955

Gnomad EAS

AF:

0.459

Gnomad SAS

AF:

0.242

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.223

Gnomad OTH

AF:

0.215

GnomAD3 exomes

AF:

0.261

AC:

65410

AN:

250214

Hom.:

9935

AF XY:

0.254

AC XY:

34412

AN XY:

135250

show subpopulations

Gnomad AFR exome

AF:

0.149

Gnomad AMR exome

AF:

0.406

Gnomad ASJ exome

AF:

0.108

Gnomad EAS exome

AF:

0.464

Gnomad SAS exome

AF:

0.238

Gnomad FIN exome

AF:

0.257

Gnomad NFE exome

AF:

0.222

Gnomad OTH exome

AF:

0.237

GnomAD4 exome

AF:

0.234

AC:

341825

AN:

1461210

Hom.:

42535

Cov.:

AF XY:

0.234

AC XY:

169815

AN XY:

726922

show subpopulations

Gnomad4 AFR exome

AF:

0.146

Gnomad4 AMR exome

AF:

0.398

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.425

Gnomad4 SAS exome

AF:

0.243

Gnomad4 FIN exome

AF:

0.257

Gnomad4 NFE exome

AF:

0.225

Gnomad4 OTH exome

AF:

0.232

GnomAD4 genome

AF:

0.220

AC:

33406

AN:

151874

Hom.:

4079

Cov.:

AF XY:

0.226

AC XY:

16753

AN XY:

74212

show subpopulations

Gnomad4 AFR

AF:

0.152

Gnomad4 AMR

AF:

0.308

Gnomad4 ASJ

AF:

0.0955

Gnomad4 EAS

AF:

0.459

Gnomad4 SAS

AF:

0.242

Gnomad4 FIN

AF:

0.261

Gnomad4 NFE

AF:

0.223

Gnomad4 OTH

AF:

0.217

Alfa

AF:

0.220

Hom.:

7116

Bravo

AF:

0.223

TwinsUK

AF:

0.217

AC:

806

ALSPAC

AF:

0.235

AC:

906

ESP6500AA

AF:

0.158

AC:

692

ESP6500EA

AF:

0.221

AC:

1896

ExAC

AF:

0.254

AC:

30891

Asia WGS

AF:

0.344

AC:

1197

AN:

3478

EpiCase

AF:

0.206

EpiControl

AF:

0.211

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 02, 2020	This variant is associated with the following publications: (PMID: 22797727) -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Amelogenesis imperfecta hypomaturation type 2A3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Amelogenesis Imperfecta, Recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.33

T;.;T;.

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.79

.;T;T;T

MetaRNN

Benign

0.0040

T;T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Pathogenic

2.9

M;.;M;.

MutationTaster

Benign

0.0018

P;P;P;P

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.7

D;D;D;D

REVEL

Uncertain

0.53

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.016

D;D;D;D

Polyphen

1.0

D;.;D;.

Vest4

0.39

MPC

0.086

ClinPred

0.024

GERP RS

5.7

Varity_R

0.57

gMVP

0.51

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