rs690346

Variant names:

Variant summary

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

The NM_182758.4(WDR72):c.298A>G(p.Met100Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.993 in 1,608,956 control chromosomes in the GnomAD database, including 793,903 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.96 ( 70788 hom., cov: 33)

Exomes 𝑓: 1.0 ( 723115 hom. )

Consequence

WDR72
NM_182758.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.922

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=5.5697984E-7).

BP6

Variant 15-53716648-T-C is Benign according to our data. Variant chr15-53716648-T-C is described in ClinVar as [Benign]. Clinvar id is 263001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-53716648-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR72	NM_182758.4 link	c.298A>G	p.Met100Val	missense_variant	Exon 4 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.298A>G	p.Met100Val	missense_variant	Exon 4 of 20	1	NM_182758.4	ENSP00000353699.5		Q3MJ13

Frequencies

GnomAD3 genomes

AF:

0.963

AC:

146480

AN:

152130

Hom.:

70760

Cov.:

show subpopulations

Gnomad AFR

AF:

0.871

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.987

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.969

GnomAD3 exomes

AF:

0.990

AC:

248821

AN:

251214

Hom.:

123361

AF XY:

0.993

AC XY:

134800

AN XY:

135762

show subpopulations

Gnomad AFR exome

AF:

0.869

Gnomad AMR exome

AF:

0.995

Gnomad ASJ exome

AF:

0.999

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.995

GnomAD4 exome

AF:

0.996

AC:

1451151

AN:

1456708

Hom.:

723115

Cov.:

AF XY:

0.997

AC XY:

722662

AN XY:

725032

show subpopulations

Gnomad4 AFR exome

AF:

0.868

Gnomad4 AMR exome

AF:

0.994

Gnomad4 ASJ exome

AF:

0.999

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.991

GnomAD4 genome

AF:

0.963

AC:

146563

AN:

152248

Hom.:

70788

Cov.:

AF XY:

0.964

AC XY:

71733

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.870

Gnomad4 AMR

AF:

0.987

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.969

Alfa

AF:

0.992

Hom.:

117472

Bravo

AF:

0.958

TwinsUK

AF:

1.00

AC:

3708

ALSPAC

AF:

1.00

AC:

3853

ESP6500AA

AF:

0.880

AC:

3862

ESP6500EA

AF:

1.00

AC:

8585

ExAC

AF:

0.988

AC:

119977

Asia WGS

AF:

0.995

AC:

3461

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

0.999

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: 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: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.0014

T;.;T;.;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.25

.;T;T;T;T

MetaRNN

Benign

5.6e-7

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.57

N;.;N;.;.

PrimateAI

Benign

0.37

PROVEAN

Benign

1.0

N;N;N;N;N

REVEL

Benign

0.013

Sift

Benign

0.87

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

B;.;B;.;.

Vest4

0.11

MPC

0.012

ClinPred

0.0020

GERP RS

2.3

Varity_R

0.046

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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