Variant rs2276888 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_025132.4(WDR19):c.3917+80A>G variant causes a intron 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
NM_025132.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.521

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
WDR19	NM_025132.4 linkuse as main transcript	c.3917+80A>G		intron_variant		ENST00000399820.8	NP_079408.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR19	ENST00000399820.8 linkuse as main transcript	c.3917+80A>G		intron_variant		1	NM_025132.4	ENSP00000382717	P1	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

Gnomad4 AFR exome

AF:

0.153

Gnomad4 AMR exome

AF:

0.624

Gnomad4 ASJ exome

AF:

0.530

Gnomad4 EAS exome

AF:

0.630

Gnomad4 SAS exome

AF:

0.590

Gnomad4 FIN exome

AF:

0.558

Gnomad4 NFE exome

AF:

0.566

Gnomad4 OTH exome

AF:

0.538

GnomAD4 genome

AF:

0.460

AC:

69897

AN:

151902

Hom.:

18714

Cov.:

AF XY:

0.466

AC XY:

34570

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.170

Gnomad4 AMR

AF:

0.584

Gnomad4 ASJ

AF:

0.522

Gnomad4 EAS

AF:

0.620

Gnomad4 SAS

AF:

0.611

Gnomad4 FIN

AF:

0.551

Gnomad4 NFE

AF:

0.567

Gnomad4 OTH

AF:

0.488

Alfa

AF:

0.544

Hom.:

16458

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.3

DANN

Benign

0.33

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