rs557128345

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_182758.4(WDR72):​c.2686C>T​(p.Arg896*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,612,546 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 (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

WDR72
NM_182758.4 stop_gained

Scores

2
2
3

Clinical Significance

Pathogenic criteria provided, single submitter P:3

Conservation

PhyloP100: 2.54
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 15-53615520-G-A is Pathogenic according to our data. Variant chr15-53615520-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 522610.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WDR72NM_182758.4 linkuse as main transcriptc.2686C>T p.Arg896* stop_gained 15/20 ENST00000360509.10 NP_877435.3 Q3MJ13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WDR72ENST00000360509.10 linkuse as main transcriptc.2686C>T p.Arg896* stop_gained 15/201 NM_182758.4 ENSP00000353699.5 Q3MJ13
WDR72ENST00000396328.5 linkuse as main transcriptc.2686C>T p.Arg896* stop_gained 15/201 ENSP00000379619.1 Q3MJ13
WDR72ENST00000559418.5 linkuse as main transcriptc.2716C>T p.Arg906* stop_gained 14/195 ENSP00000452765.1 H0YKE0
WDR72ENST00000557913.5 linkuse as main transcriptc.2677C>T p.Arg893* stop_gained 15/205 ENSP00000453378.1 H0YLX4

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151826
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000240
AC:
6
AN:
249874
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135200
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000890
AC:
13
AN:
1460602
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
726626
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000139
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151944
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74290
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000247
AC:
3
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Amelogenesis imperfecta hypomaturation type 2A3 Pathogenic:2
Pathogenic, no assertion criteria providedresearchInstitute of Human Genetics, University of UlmApr 18, 2024- -
Pathogenic, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsMar 03, 2022- -
Amelogenesis imperfecta hypomaturation type 2A3;C5436235:Renal tubular acidosis, distal, 4, with hemolytic anemia Pathogenic:1
Pathogenic, no assertion criteria providedresearchDivision of Molecular Medicine, Faculty of Medicine Siriraj Hospital, Mahidol UniversityJan 01, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.43
D
BayesDel_noAF
Pathogenic
0.28
CADD
Pathogenic
38
DANN
Uncertain
0.99
Eigen
Uncertain
0.47
Eigen_PC
Benign
0.18
FATHMM_MKL
Benign
0.36
N
Vest4
0.30
GERP RS
3.8

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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.

Other links and lift over

dbSNP: rs557128345; hg19: chr15-53907717; COSMIC: COSV64751129; COSMIC: COSV64751129; API