rs387906983

chr4-39215913-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_025132.4(WDR19):c.1034T>G(p.Val345Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR19 NM_025132.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.77

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 4-39215913-T-G is Pathogenic according to our data. Variant chr4-39215913-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 30706.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-39215913-T-G is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR19	NM_025132.4	c.1034T>G	p.Val345Gly	missense_variant	11/37	ENST00000399820.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR19	ENST00000399820.8	c.1034T>G	p.Val345Gly	missense_variant	11/37	1	NM_025132.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Nephronophthisis 13 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 11, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.56	D
BayesDel_noAF	Pathogenic	0.57
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D;.
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Pathogenic	0.49	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Pathogenic	0.85	D
MutationAssessor	Pathogenic	3.0	M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.2	D;D
REVEL	Pathogenic	0.86
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.042	D;T
Polyphen		0.27	B;B
Vest4		0.51
MutPred		0.77		Loss of stability (P = 0.008);Loss of stability (P = 0.008);
MVP		0.97
MPC		0.25
ClinPred		0.99	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.83
gMVP		0.89

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

Other links and lift over

dbSNP: rs387906983; hg19: chr4-39217533;