4-39224999-T-G

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_025132.4(WDR19):c.1595T>G(p.Ile532Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000829 in 1,567,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I532T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000085 ( 0 hom. )

Consequence

WDR19
NM_025132.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.19

Publications

0 publications found

Variant links:

Genes affected

WDR19 (HGNC:18340): (WD repeat domain 19) The protein encoded by this gene is a member of the WD (tryptophan-aspartic acid) repeat family, which is a large family of structurally-related proteins known to participate in a wide range of cellular processes. Each WD repeat typically contains about 40 amino acids that are usually bracketed by glycine-histidine and tryptophan-aspartic acid (WD) dipeptides. This protein contains six WD repeats, three transmembrane domains, and a clathrin heavy-chain repeat. Mutations in this gene have been described in individuals with a wide range of disorders affecting function of the cilium. These disorders are known as ciliopathies, and include Jeune syndrome, Sensenbrenner syndromes, Senior-Loken syndrome, combined or isolated nephronophthisis (NPHP), and retinitis pigmentosa (RP). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

WDR19 Gene-Disease associations (from GenCC):

asphyxiating thoracic dystrophy 5
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
cranioectodermal dysplasia 4
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
nephronophthisis 13
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Senior-Loken syndrome 8
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
cranioectodermal dysplasia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Jeune syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
nephronophthisis 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Senior-Loken syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

WDR19 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.964

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025132.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR19	NM_025132.4	MANE Select	c.1595T>G	p.Ile532Ser	missense	Exon 15 of 37	NP_079408.3
	WDR19	NM_001317924.2		c.1115T>G	p.Ile372Ser	missense	Exon 14 of 36	NP_001304853.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
WDR19	ENST00000399820.8	TSL:1 MANE Select	c.1595T>G	p.Ile532Ser	missense	Exon 15 of 37	ENSP00000382717.3
WDR19	ENST00000506869.5	TSL:2	n.*1176T>G		non_coding_transcript_exon	Exon 14 of 36	ENSP00000424319.1
WDR19	ENST00000512095.5	TSL:2	n.593T>G		non_coding_transcript_exon	Exon 5 of 23

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000161

AC:

AN:

186620

AF XY:

0.0000101

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000848

AC:

AN:

1415744

Hom.:

Cov.:

AF XY:

0.0000143

AC XY:

AN XY:

700066

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32118

American (AMR)

AF:

0.00

AC:

AN:

36164

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25278

East Asian (EAS)

AF:

0.00

AC:

AN:

38644

South Asian (SAS)

AF:

0.000141

AC:

AN:

77752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5616

European-Non Finnish (NFE)

AF:

9.17e-7

AC:

AN:

1090146

Other (OTH)

AF:

0.00

AC:

AN:

58664

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000250

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.50

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.52

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.41

MetaRNN

Pathogenic

0.96

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

2.9

PhyloP100

7.2

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-4.8

REVEL

Pathogenic

0.93

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.039

Polyphen

0.99

Vest4

0.94

MutPred

0.86

Gain of disorder (P = 0.0024)

MVP

0.99

MPC

0.64

ClinPred

0.96

GERP RS

6.0

Varity_R

0.94

gMVP

0.94

Mutation Taster

=76/24

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over