Variant 15-53615684-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_182758.4(WDR72):c.2522T>A(p.Leu841Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

WDR72
NM_182758.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.89

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:

WDR72 (HGNC:):

WDR72 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.858

PP5

Variant 15-53615684-A-T is Pathogenic according to our data. Variant chr15-53615684-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 522609.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR72	NM_182758.4 linkuse as main transcript	c.2522T>A	p.Leu841Gln	missense_variant	15/20	ENST00000360509.10	NP_877435.3	Q3MJ13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WDR72	ENST00000360509.10 linkuse as main transcript	c.2522T>A	p.Leu841Gln	missense_variant	15/20	1	NM_182758.4	ENSP00000353699.5	Q3MJ13
WDR72	ENST00000396328.5 linkuse as main transcript	c.2522T>A	p.Leu841Gln	missense_variant	15/20	1		ENSP00000379619.1	Q3MJ13
WDR72	ENST00000559418.5 linkuse as main transcript	c.2552T>A	p.Leu851Gln	missense_variant	14/19	5		ENSP00000452765.1	H0YKE0
WDR72	ENST00000557913.5 linkuse as main transcript	c.2513T>A	p.Leu838Gln	missense_variant	15/20	5		ENSP00000453378.1	H0YLX4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000805

AC:

AN:

248410

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134496

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459736

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726028

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Renal tubular acidosis, distal, 4, with hemolytic anemia

Pathogenic:1

Pathogenic, no assertion criteria provided

research

Division of Molecular Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University

Jan 01, 2018

This variant was observed in compound heterozygity with NM_182758.3:c.1777A>G and is pathogenic for autosomal recessive OMIM:611590. These variants were observed by whole exome sequencing and Sanger sequencing in three patients. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Pathogenic

0.26

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

T;.;T;.

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

.;T;T;T

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.86

D;D;D;D

MetaSVM

Uncertain

0.095

MutationAssessor

Uncertain

2.9

M;.;M;.

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-5.6

D;D;D;D

REVEL

Uncertain

0.61

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;.;D;.

Vest4

0.97

MutPred

0.58

Loss of sheet (P = 0.0043);.;Loss of sheet (P = 0.0043);.;

MVP

0.86

MPC

0.088

ClinPred

0.99

GERP RS

5.7

Varity_R

0.90

gMVP

0.79

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

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