rs551225

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.917C>T(p.Pro306Leu) variant causes a missense change. The variant allele was found at a frequency of 0.456 in 1,611,968 control chromosomes in the GnomAD database, including 173,557 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 12394 hom., cov: 33)

Exomes 𝑓: 0.46 ( 161163 hom. )

Consequence

WDR72
NM_182758.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.45

Publications

30 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=0.0017650723).

BP6

Variant 15-53710894-G-A is Benign according to our data. Variant chr15-53710894-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 263003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR72	NM_182758.4 link	c.917C>T	p.Pro306Leu	missense_variant	Exon 9 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.917C>T	p.Pro306Leu	missense_variant	Exon 9 of 20	1	NM_182758.4	ENSP00000353699.5		Q3MJ13

Frequencies

GnomAD3 genomes

AF:

0.381

AC:

57869

AN:

151968

Hom.:

12400

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.596

Gnomad AMR

AF:

0.372

Gnomad ASJ

AF:

0.626

Gnomad EAS

AF:

0.206

Gnomad SAS

AF:

0.461

Gnomad FIN

AF:

0.319

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.487

Gnomad OTH

AF:

0.425

GnomAD2 exomes

AF:

0.410

AC:

102877

AN:

251010

AF XY:

0.424

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.305

Gnomad ASJ exome

AF:

0.615

Gnomad EAS exome

AF:

0.193

Gnomad FIN exome

AF:

0.333

Gnomad NFE exome

AF:

0.484

Gnomad OTH exome

AF:

0.453

GnomAD4 exome

AF:

0.464

AC:

676833

AN:

1459882

Hom.:

161163

Cov.:

AF XY:

0.465

AC XY:

338080

AN XY:

726388

show subpopulations

African (AFR)

AF:

0.207

AC:

6924

AN:

33454

American (AMR)

AF:

0.312

AC:

13935

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.614

AC:

16035

AN:

26124

East Asian (EAS)

AF:

0.253

AC:

10057

AN:

39692

South Asian (SAS)

AF:

0.463

AC:

39901

AN:

86216

European-Finnish (FIN)

AF:

0.342

AC:

18204

AN:

53238

Middle Eastern (MID)

AF:

0.551

AC:

3174

AN:

5764

European-Non Finnish (NFE)

AF:

0.487

AC:

541151

AN:

1110344

Other (OTH)

AF:

0.455

AC:

27452

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

17031

34062

51092

68123

85154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15660

31320

46980

62640

78300

<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:

0.380

AC:

57855

AN:

152086

Hom.:

12394

Cov.:

AF XY:

0.373

AC XY:

27757

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.208

AC:

8633

AN:

41492

American (AMR)

AF:

0.371

AC:

5667

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.626

AC:

2172

AN:

3468

East Asian (EAS)

AF:

0.206

AC:

1067

AN:

5172

South Asian (SAS)

AF:

0.461

AC:

2227

AN:

4826

European-Finnish (FIN)

AF:

0.319

AC:

3372

AN:

10574

Middle Eastern (MID)

AF:

0.602

AC:

177

AN:

294

European-Non Finnish (NFE)

AF:

0.487

AC:

33112

AN:

67972

Other (OTH)

AF:

0.421

AC:

889

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1745

3490

5235

6980

8725

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

554

1108

1662

2216

2770

<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:

0.451

Hom.:

49575

Bravo

AF:

0.373

TwinsUK

AF:

0.486

AC:

1801

ALSPAC

AF:

0.486

AC:

1873

ESP6500AA

AF:

0.216

AC:

949

ESP6500EA

AF:

0.501

AC:

4304

ExAC

AF:

0.411

AC:

49909

Asia WGS

AF:

0.307

AC:

1067

AN:

3478

EpiCase

AF:

0.508

EpiControl

AF:

0.505

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

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 30476138) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

Uncertain

0.50

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;.;T;.;.

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.91

.;D;D;D;D

MetaRNN

Benign

0.0018

T;T;T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.3

M;.;M;.;.

PhyloP100

6.5

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-5.1

D;D;D;D;D

REVEL

Benign

0.29

Sift

Uncertain

0.012

D;T;D;T;D

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0

D;.;D;.;.

Vest4

0.67

MPC

0.088

ClinPred

0.014

GERP RS

5.6

Varity_R

0.42

gMVP

0.65

Mutation Taster

=89/11

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