17-82627157-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_019613.4(WDR45B):c.332+47A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 1,416,574 control chromosomes in the GnomAD database, including 447,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (51516 hom., cov: 35)
  • Exomes 𝑓: 0.79 (395850 hom.)
• Consequence: WDR45B NM_019613.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.952

Genes affected

WDR45B (HGNC:25072): (WD repeat domain 45B) This gene encodes a member of the WIPI or SVP1 family of WD40 repeat-containing proteins. The protein contains seven WD40 repeats that are thought to fold into a beta-propeller structure that mediates protein-protein interactions, and a conserved motif for interaction with phospholipids. The human genome contains several pseudogenes of this gene. [provided by RefSeq, Jul 2008]

FOXK2 (HGNC:6036): (forkhead box K2) The protein encoded by this gene contains a fork head DNA binding domain. This protein can bind to the purine-rich motifs of the HIV long terminal repeat (LTR), and to the similar purine-rich motif in the interleukin 2 (IL2) promoter. It may be involved in the regulation of viral and cellular promoter elements. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 17-82627157-T-A is Benign according to our data. Variant chr17-82627157-T-A is described in ClinVar as [Benign]. Clinvar id is 1684229.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR45B	NM_019613.4	c.332+47A>T		intron_variant		ENST00000392325.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR45B	ENST00000392325.9	c.332+47A>T		intron_variant		1	NM_019613.4	P1

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124784 AN: 152154 Hom.: 51463 Cov.: 35

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.894

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.907

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.829

GnomAD3 exomes AF: 0.814 AC: 203925 AN: 250608 Hom.: 83534 AF XY: 0.816 AC XY: 110547 AN XY: 135528

Gnomad AFR exome AF: 0.899

Gnomad AMR exome AF: 0.831

Gnomad ASJ exome AF: 0.898

Gnomad EAS exome AF: 0.783

Gnomad SAS exome AF: 0.914

Gnomad FIN exome AF: 0.762

Gnomad NFE exome AF: 0.777

Gnomad OTH exome AF: 0.808

GnomAD4 exome AF: 0.790 AC: 998171 AN: 1264302 Hom.: 395850 Cov.: 18 AF XY: 0.794 AC XY: 507423 AN XY: 639354

Gnomad4 AFR exome AF: 0.904

Gnomad4 AMR exome AF: 0.831

Gnomad4 ASJ exome AF: 0.892

Gnomad4 EAS exome AF: 0.789

Gnomad4 SAS exome AF: 0.912

Gnomad4 FIN exome AF: 0.760

Gnomad4 NFE exome AF: 0.770

Gnomad4 OTH exome AF: 0.811

GnomAD4 genome AF: 0.820 AC: 124898 AN: 152272 Hom.: 51516 Cov.: 35 AF XY: 0.822 AC XY: 61224 AN XY: 74456

Gnomad4 AFR AF: 0.894

Gnomad4 AMR AF: 0.829

Gnomad4 ASJ AF: 0.894

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.908

Gnomad4 FIN AF: 0.767

Gnomad4 NFE AF: 0.775

Gnomad4 OTH AF: 0.830

Alfa AF: 0.807 Hom.: 9106

Bravo AF: 0.828

Asia WGS AF: 0.879 AC: 3053 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.023
Dann	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2291392; hg19: chr17-80585033; COSMIC: COSV66408010; COSMIC: COSV66408010;