dbSNP rs34828731: WDR72:c.261-8delT (chr15-53716692-GA-G) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_182758.4(WDR72):c.261-8delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13856 hom., cov: 0)

Exomes 𝑓: 0.46 ( 153048 hom. )

Consequence

WDR72
NM_182758.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.00

Publications

6 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 -16 ACMG points.

BP6

Variant 15-53716692-GA-G is Benign according to our data. Variant chr15-53716692-GA-G is described in ClinVar as [Likely_benign]. Clinvar id is 263000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR72	NM_182758.4 link	c.261-8delT		splice_region_variant, intron_variant	Intron 3 of 19	ENST00000360509.10	NP_877435.3	Q3MJ13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR72	ENST00000360509.10 link	c.261-8delT		splice_region_variant, intron_variant	Intron 3 of 19	1	NM_182758.4	ENSP00000353699.5		Q3MJ13

Frequencies

GnomAD3 genomes

AF:

0.417

AC:

63326

AN:

151764

Hom.:

13862

Cov.:

show subpopulations

Gnomad AFR

AF:

0.359

Gnomad AMI

AF:

0.596

Gnomad AMR

AF:

0.380

Gnomad ASJ

AF:

0.624

Gnomad EAS

AF:

0.203

Gnomad SAS

AF:

0.458

Gnomad FIN

AF:

0.311

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.476

Gnomad OTH

AF:

0.443

GnomAD2 exomes

AF:

0.414

AC:

103837

AN:

250714

AF XY:

0.425

show subpopulations

Gnomad AFR exome

AF:

0.356

Gnomad AMR exome

AF:

0.308

Gnomad ASJ exome

AF:

0.612

Gnomad EAS exome

AF:

0.189

Gnomad FIN exome

AF:

0.326

Gnomad NFE exome

AF:

0.475

Gnomad OTH exome

AF:

0.449

GnomAD4 exome

AF:

0.456

AC:

654682

AN:

1436560

Hom.:

153048

Cov.:

AF XY:

0.457

AC XY:

327497

AN XY:

716052

show subpopulations

African (AFR)

AF:

0.360

AC:

11897

AN:

33068

American (AMR)

AF:

0.315

AC:

14066

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.610

AC:

15815

AN:

25926

East Asian (EAS)

AF:

0.244

AC:

9653

AN:

39618

South Asian (SAS)

AF:

0.459

AC:

39361

AN:

85726

European-Finnish (FIN)

AF:

0.333

AC:

17764

AN:

53368

Middle Eastern (MID)

AF:

0.556

AC:

3177

AN:

5718

European-Non Finnish (NFE)

AF:

0.474

AC:

515797

AN:

1088892

Other (OTH)

AF:

0.456

AC:

27152

AN:

59568

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

16164

32328

48491

64655

80819

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.417

AC:

63329

AN:

151882

Hom.:

13856

Cov.:

AF XY:

0.408

AC XY:

30306

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.359

AC:

14858

AN:

41424

American (AMR)

AF:

0.380

AC:

5795

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.624

AC:

2165

AN:

3470

East Asian (EAS)

AF:

0.203

AC:

1048

AN:

5160

South Asian (SAS)

AF:

0.459

AC:

2206

AN:

4808

European-Finnish (FIN)

AF:

0.311

AC:

3280

AN:

10554

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.476

AC:

32331

AN:

67886

Other (OTH)

AF:

0.439

AC:

926

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1816

3632

5447

7263

9079

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.468

Hom.:

3128

Bravo

AF:

0.416

Asia WGS

AF:

0.313

AC:

1088

AN:

3478

EpiCase

AF:

0.499

EpiControl

AF:

0.498

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

not provided

Benign:1

Nov 12, 2018

GeneDx

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

PhyloP100

0.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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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rs34828731

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