rs2167494

Positions:

chr4-39214601-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_025132.4(WDR19):c.891C>T(p.Cys297Cys) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,509,908 control chromosomes in the GnomAD database, including 66,124 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 6791 hom., cov: 31)

Exomes 𝑓: 0.29 ( 59333 hom. )

Consequence

WDR19
NM_025132.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0005476

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 1.52

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 links:

WDR19 (HGNC:):

WDR19 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 4-39214601-C-T is Benign according to our data. Variant chr4-39214601-C-T is described in ClinVar as [Benign]. Clinvar id is 261867.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-39214601-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.52 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR19	NM_025132.4 linkuse as main transcript	c.891C>T	p.Cys297Cys	splice_region_variant, synonymous_variant	10/37	ENST00000399820.8	NP_079408.3	Q8NEZ3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR19	ENST00000399820.8 linkuse as main transcript	c.891C>T	p.Cys297Cys	splice_region_variant, synonymous_variant	10/37	1	NM_025132.4	ENSP00000382717.3		Q8NEZ3-1

Frequencies

GnomAD3 genomes

AF:

0.298

AC:

45187

AN:

151540

Hom.:

6783

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.397

Gnomad AMR

AF:

0.271

Gnomad ASJ

AF:

0.303

Gnomad EAS

AF:

0.168

Gnomad SAS

AF:

0.282

Gnomad FIN

AF:

0.299

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.312

Gnomad OTH

AF:

0.305

GnomAD3 exomes

AF:

0.286

AC:

64441

AN:

225264

Hom.:

9463

AF XY:

0.289

AC XY:

35318

AN XY:

122298

show subpopulations

Gnomad AFR exome

AF:

0.293

Gnomad AMR exome

AF:

0.236

Gnomad ASJ exome

AF:

0.293

Gnomad EAS exome

AF:

0.157

Gnomad SAS exome

AF:

0.298

Gnomad FIN exome

AF:

0.298

Gnomad NFE exome

AF:

0.312

Gnomad OTH exome

AF:

0.285

GnomAD4 exome

AF:

0.292

AC:

396569

AN:

1358250

Hom.:

59333

Cov.:

AF XY:

0.293

AC XY:

198605

AN XY:

677786

show subpopulations

Gnomad4 AFR exome

AF:

0.283

Gnomad4 AMR exome

AF:

0.245

Gnomad4 ASJ exome

AF:

0.292

Gnomad4 EAS exome

AF:

0.175

Gnomad4 SAS exome

AF:

0.296

Gnomad4 FIN exome

AF:

0.296

Gnomad4 NFE exome

AF:

0.298

Gnomad4 OTH exome

AF:

0.292

GnomAD4 genome

AF:

0.298

AC:

45211

AN:

151658

Hom.:

6791

Cov.:

AF XY:

0.294

AC XY:

21781

AN XY:

74070

show subpopulations

Gnomad4 AFR

AF:

0.301

Gnomad4 AMR

AF:

0.271

Gnomad4 ASJ

AF:

0.303

Gnomad4 EAS

AF:

0.168

Gnomad4 SAS

AF:

0.283

Gnomad4 FIN

AF:

0.299

Gnomad4 NFE

AF:

0.312

Gnomad4 OTH

AF:

0.300

Alfa

AF:

0.306

Hom.:

11569

Bravo

AF:

0.298

Asia WGS

AF:

0.218

AC:

757

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Asphyxiating thoracic dystrophy 5

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Cranioectodermal dysplasia 4

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

Nephronophthisis 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Senior-Loken syndrome 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Asphyxiating thoracic dystrophy 5;C4225376:Senior-Loken syndrome 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00055

dbscSNV1_RF

Benign

0.022

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