19-33137718-C-A

Position:

• chr19-33137718-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_173479.4(WDR88):​c.318C>A​(p.Ser106Arg) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR88 NM_173479.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.42

Genes affected

WDR88 (HGNC:26999): (WD repeat domain 88)

WDR88 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.762

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR88	NM_173479.4	c.318C>A	p.Ser106Arg	missense_variant	2/11	ENST00000355868.4	NP_775750.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR88	ENST00000355868.4	c.318C>A	p.Ser106Arg	missense_variant	2/11	2	NM_173479.4	ENSP00000348129.2
WDR88	ENST00000361680.6	c.318C>A	p.Ser106Arg	missense_variant	2/12	1		ENSP00000355148.2
WDR88	ENST00000592765.5	c.318C>A	p.Ser106Arg	missense_variant	2/6	5		ENSP00000467383.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 26, 2024

The c.318C>A (p.S106R) alteration is located in exon 2 (coding exon 2) of the WDR88 gene. This alteration results from a C to A substitution at nucleotide position 318, causing the serine (S) at amino acid position 106 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	7.3
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0029	.;.;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.76	D;D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.21	.;N;N
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.8	.;D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.015	.;D;T
Sift4G	Uncertain	0.0060	D;T;D
Polyphen		0.98	.;.;D
Vest4		0.75
MutPred		0.53		Gain of methylation at S106 (P = 0.102);Gain of methylation at S106 (P = 0.102);Gain of methylation at S106 (P = 0.102);
MVP		0.072
MPC		0.94
ClinPred		0.96	D
GERP RS		-2.2
Varity_R		0.37
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-33628624;