rs17730281

Variant names:

Variant summary

Our verdict is Benign. The variant received -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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L819P) has been classified as Uncertain significance.

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

Publications

44 publications found

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 Gene-Disease associations (from GenCC):

amelogenesis imperfecta
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
amelogenesis imperfecta hypomaturation type 2A3
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
amelogenesis imperfecta type 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
renal tubular acidosis
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

WDR72 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 262999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
WDR72	NM_182758.4 link	c.2455C>T	p.Leu819Phe	missense_variant	Exon 15 of 20	ENST00000360509.10	NP_877435.3	Q3MJ13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR72	ENST00000360509.10 link	c.2455C>T	p.Leu819Phe	missense_variant	Exon 15 of 20	1	NM_182758.4	ENSP00000353699.5		Q3MJ13

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

GnomAD2 exomes

AF:

0.261

AC:

65410

AN:

250214

AF XY:

0.254

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 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

African (AFR)

AF:

0.146

AC:

4874

AN:

33450

American (AMR)

AF:

0.398

AC:

17742

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

2689

AN:

26110

East Asian (EAS)

AF:

0.425

AC:

16858

AN:

39688

South Asian (SAS)

AF:

0.243

AC:

20945

AN:

86230

European-Finnish (FIN)

AF:

0.257

AC:

13725

AN:

53396

Middle Eastern (MID)

AF:

0.147

AC:

846

AN:

5764

European-Non Finnish (NFE)

AF:

0.225

AC:

250171

AN:

1111586

Other (OTH)

AF:

0.232

AC:

13975

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

15537

31074

46611

62148

77685

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8722

17444

26166

34888

43610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.220

AC:

33406

AN:

151874

Hom.:

4079

Cov.:

AF XY:

0.226

AC XY:

16753

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.152

AC:

6290

AN:

41450

American (AMR)

AF:

0.308

AC:

4683

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.0955

AC:

331

AN:

3466

East Asian (EAS)

AF:

0.459

AC:

2365

AN:

5150

South Asian (SAS)

AF:

0.242

AC:

1168

AN:

4824

European-Finnish (FIN)

AF:

0.261

AC:

2752

AN:

10546

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.223

AC:

15173

AN:

67896

Other (OTH)

AF:

0.217

AC:

459

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1317

2634

3950

5267

6584

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

370

740

1110

1480

1850

<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:

0.223

Hom.:

15168

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 02, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 22797727) -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Amelogenesis imperfecta hypomaturation type 2A3

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Amelogenesis Imperfecta, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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;.

PhyloP100

2.1

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

Mutation Taster

=97/3

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over