rs2276888

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000510315.1(WDR19):n.17A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 1,324,962 control chromosomes in the GnomAD database, including 205,780 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 18714 hom., cov: 31)

Exomes 𝑓: 0.56 ( 187066 hom. )

Consequence

WDR19
ENST00000510315.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.521

Publications

14 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 4-39278287-A-G is Benign according to our data. Variant chr4-39278287-A-G is described in ClinVar as Benign. ClinVar VariationId is 1238547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR19	NM_025132.4 link	c.3917+80A>G		intron_variant	Intron 35 of 36	ENST00000399820.8	NP_079408.3	Q8NEZ3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR19	ENST00000399820.8 link	c.3917+80A>G		intron_variant	Intron 35 of 36	1	NM_025132.4	ENSP00000382717.3		Q8NEZ3-1

Frequencies

GnomAD3 genomes

AF:

0.461

AC:

69898

AN:

151782

Hom.:

18716

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.542

Gnomad AMR

AF:

0.584

Gnomad ASJ

AF:

0.522

Gnomad EAS

AF:

0.621

Gnomad SAS

AF:

0.611

Gnomad FIN

AF:

0.551

Gnomad MID

AF:

0.560

Gnomad NFE

AF:

0.567

Gnomad OTH

AF:

0.489

GnomAD4 exome

AF:

0.559

AC:

656012

AN:

1173060

Hom.:

187066

Cov.:

AF XY:

0.561

AC XY:

329290

AN XY:

586960

show subpopulations

African (AFR)

AF:

0.153

AC:

3891

AN:

25352

American (AMR)

AF:

0.624

AC:

14866

AN:

23836

Ashkenazi Jewish (ASJ)

AF:

0.530

AC:

12006

AN:

22664

East Asian (EAS)

AF:

0.630

AC:

21825

AN:

34630

South Asian (SAS)

AF:

0.590

AC:

40127

AN:

68056

European-Finnish (FIN)

AF:

0.558

AC:

27490

AN:

49238

Middle Eastern (MID)

AF:

0.521

AC:

2719

AN:

5216

European-Non Finnish (NFE)

AF:

0.566

AC:

505959

AN:

893614

Other (OTH)

AF:

0.538

AC:

27129

AN:

50454

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

13907

27815

41722

55630

69537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13204

26408

39612

52816

66020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.460

AC:

69897

AN:

151902

Hom.:

18714

Cov.:

AF XY:

0.466

AC XY:

34570

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.170

AC:

7028

AN:

41418

American (AMR)

AF:

0.584

AC:

8907

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.522

AC:

1810

AN:

3468

East Asian (EAS)

AF:

0.620

AC:

3192

AN:

5150

South Asian (SAS)

AF:

0.611

AC:

2937

AN:

4810

European-Finnish (FIN)

AF:

0.551

AC:

5811

AN:

10548

Middle Eastern (MID)

AF:

0.548

AC:

161

AN:

294

European-Non Finnish (NFE)

AF:

0.567

AC:

38532

AN:

67956

Other (OTH)

AF:

0.488

AC:

1025

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1659

3319

4978

6638

8297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.541

Hom.:

19210

Bravo

AF:

0.449

Asia WGS

AF:

0.573

AC:

1994

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 16, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.3

(source)

DANN

Benign

0.33

PhyloP100

0.52

Mutation Taster

=100/0

polymorphism (auto)

(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

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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