15-53702296-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_182758.4(WDR72):c.1407T>C(p.Tyr469Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 1,613,322 control chromosomes in the GnomAD database, including 237,461 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27141 hom., cov: 31)

Exomes 𝑓: 0.53 ( 210320 hom. )

Consequence

WDR72
NM_182758.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.19

Publications

17 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 15-53702296-A-G is Benign according to our data. Variant chr15-53702296-A-G is described in ClinVar as [Benign]. Clinvar id is 262998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.19 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR72	NM_182758.4 link	c.1407T>C	p.Tyr469Tyr	synonymous_variant	Exon 12 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.1407T>C	p.Tyr469Tyr	synonymous_variant	Exon 12 of 20	1	NM_182758.4	ENSP00000353699.5		Q3MJ13

Frequencies

GnomAD3 genomes

AF:

0.589

AC:

89411

AN:

151856

Hom.:

27104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.684

Gnomad AMI

AF:

0.384

Gnomad AMR

AF:

0.616

Gnomad ASJ

AF:

0.394

Gnomad EAS

AF:

0.798

Gnomad SAS

AF:

0.533

Gnomad FIN

AF:

0.690

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.512

Gnomad OTH

AF:

0.545

GnomAD2 exomes

AF:

0.583

AC:

146603

AN:

251414

AF XY:

0.571

show subpopulations

Gnomad AFR exome

AF:

0.683

Gnomad AMR exome

AF:

0.698

Gnomad ASJ exome

AF:

0.406

Gnomad EAS exome

AF:

0.809

Gnomad FIN exome

AF:

0.675

Gnomad NFE exome

AF:

0.514

Gnomad OTH exome

AF:

0.539

GnomAD4 exome

AF:

0.532

AC:

777548

AN:

1461348

Hom.:

210320

Cov.:

AF XY:

0.530

AC XY:

385673

AN XY:

727002

show subpopulations

African (AFR)

AF:

0.682

AC:

22815

AN:

33470

American (AMR)

AF:

0.689

AC:

30820

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.408

AC:

10667

AN:

26126

East Asian (EAS)

AF:

0.749

AC:

29712

AN:

39678

South Asian (SAS)

AF:

0.528

AC:

45502

AN:

86238

European-Finnish (FIN)

AF:

0.666

AC:

35571

AN:

53402

Middle Eastern (MID)

AF:

0.427

AC:

2460

AN:

5766

European-Non Finnish (NFE)

AF:

0.511

AC:

567571

AN:

1111578

Other (OTH)

AF:

0.537

AC:

32430

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

18423

36846

55269

73692

92115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16620

33240

49860

66480

83100

<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:

0.589

AC:

89510

AN:

151974

Hom.:

27141

Cov.:

AF XY:

0.597

AC XY:

44345

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.684

AC:

28356

AN:

41436

American (AMR)

AF:

0.617

AC:

9411

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.394

AC:

1366

AN:

3470

East Asian (EAS)

AF:

0.798

AC:

4122

AN:

5166

South Asian (SAS)

AF:

0.533

AC:

2560

AN:

4806

European-Finnish (FIN)

AF:

0.690

AC:

7281

AN:

10554

Middle Eastern (MID)

AF:

0.381

AC:

112

AN:

294

European-Non Finnish (NFE)

AF:

0.512

AC:

34798

AN:

67976

Other (OTH)

AF:

0.548

AC:

1155

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1821

3642

5463

7284

9105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

752

1504

2256

3008

3760

<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:

0.534

Hom.:

78141

Bravo

AF:

0.592

Asia WGS

AF:

0.699

AC:

2433

AN:

3478

EpiCase

AF:

0.490

EpiControl

AF:

0.492

ClinVar

Significance: 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:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

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

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

1.7

(source)

DANN

Benign

0.25

PhyloP100

1.2

Mutation Taster

=100/0

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