NM_025132.4:c.682C>G

Variant names:

• chr4-39205232-C-G
• rs587777350
• NM_025132.4:c.682C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025132.4(WDR19):​c.682C>G​(p.Gln228Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR19 NM_025132.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.51
• Publications: 0 publications found

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: G2P, Labcorp Genetics (formerly Invitae)
• 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21585494).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025132.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR19	NM_025132.4	MANE Select	c.682C>G	p.Gln228Glu	missense	Exon 8 of 37	NP_079408.3
	WDR19	NM_001317924.2		c.202C>G	p.Gln68Glu	missense	Exon 7 of 36	NP_001304853.1	B4DGR6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR19	ENST00000399820.8	TSL:1 MANE Select	c.682C>G	p.Gln228Glu	missense	Exon 8 of 37	ENSP00000382717.3	Q8NEZ3-1
	WDR19	ENST00000503697.5	TSL:1	n.*150C>G		non_coding_transcript_exon	Exon 6 of 9	ENSP00000423706.1	D6RCF7
	WDR19	ENST00000503697.5	TSL:1	n.*150C>G		3_prime_UTR	Exon 6 of 9	ENSP00000423706.1	D6RCF7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.5
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.23
Sift	Benign	0.030	D
Sift4G	Uncertain	0.015	D
Polyphen		0.010	B
Vest4		0.13
MutPred		0.55		Gain of disorder (P = 0.0926)
MVP		0.50
MPC		0.21
ClinPred		0.91	D
GERP RS		5.7
Varity_R		0.39
gMVP		0.47
Mutation Taster		=33/67	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs587777350; hg19: chr4-39206852;