19-33137707-C-T

Position:

• chr19-33137707-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173479.4(WDR88):​c.307C>T​(p.His103Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,736 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: WDR88 NM_173479.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.805

Genes affected

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

WDR88 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36823657).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR88	NM_173479.4	c.307C>T	p.His103Tyr	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.307C>T	p.His103Tyr	missense_variant	2/11	2	NM_173479.4	ENSP00000348129.2
WDR88	ENST00000361680.6	c.307C>T	p.His103Tyr	missense_variant	2/12	1		ENSP00000355148.2
WDR88	ENST00000592765.5	c.307C>T	p.His103Tyr	missense_variant	2/6	5		ENSP00000467383.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461736 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727162

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jun 18, 2021

The c.307C>T (p.H103Y) alteration is located in exon 2 (coding exon 2) of the WDR88 gene. This alteration results from a C to T substitution at nucleotide position 307, causing the histidine (H) at amino acid position 103 to be replaced by a tyrosine (Y). 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	Benign	0.13
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	.;.;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.94	.;L;L
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.0	.;D;D
REVEL	Benign	0.23
Sift	Benign	0.095	.;T;T
Sift4G	Uncertain	0.010	D;T;T
Polyphen		0.97	.;.;D
Vest4		0.36
MutPred		0.57		Gain of phosphorylation at H103 (P = 0.0542);Gain of phosphorylation at H103 (P = 0.0542);Gain of phosphorylation at H103 (P = 0.0542);
MVP		0.34
MPC		0.33
ClinPred		0.82	D
GERP RS		4.0
Varity_R		0.13
gMVP		0.13

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: rs931699319; hg19: chr19-33628613;