Variant rs751386429 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2PM5BP4_Moderate

The NM_025132.4(WDR19):c.2777G>A(p.Ser926Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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. S926I) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

WDR19
NM_025132.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.77

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr4-39253193-G-T is described in Lovd as [Pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.073423).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR19	NM_025132.4 linkuse as main transcript	c.2777G>A	p.Ser926Asn	missense_variant	25/37	ENST00000399820.8	NP_079408.3	Q8NEZ3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WDR19	ENST00000399820.8 linkuse as main transcript	c.2777G>A	p.Ser926Asn	missense_variant	25/37	1	NM_025132.4	ENSP00000382717.3	Q8NEZ3-1
WDR19	ENST00000506869.5 linkuse as main transcript	n.*2358G>A		non_coding_transcript_exon_variant	24/36	2		ENSP00000424319.1	D6RBA0
WDR19	ENST00000512095.5 linkuse as main transcript	n.1775G>A		non_coding_transcript_exon_variant	15/23	2
WDR19	ENST00000506869.5 linkuse as main transcript	n.*2358G>A		3_prime_UTR_variant	24/36	2		ENSP00000424319.1	D6RBA0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248214

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134660

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:

0.00

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460736

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726570

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:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.11

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.026

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.81

M_CAP

Benign

0.0084

MetaRNN

Benign

0.073

MetaSVM

Benign

-0.87

MutationAssessor

Benign

-0.095

PrimateAI

Benign

0.47

PROVEAN

Benign

0.49

REVEL

Uncertain

0.34

Sift

Benign

0.63

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.12

MutPred

0.28

Gain of MoRF binding (P = 0.1241);

MVP

0.69

MPC

0.16

ClinPred

0.32

GERP RS

5.5

Varity_R

0.12

gMVP

0.31

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over