17-82616656-A-G

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.807-11T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,613,790 control chromosomes in the GnomAD database, including 49,483 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3628 hom., cov: 33)
  • Exomes 𝑓: 0.25 (45855 hom.)
• Consequence: WDR45B NM_019613.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00006340
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.41

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=-0.81).
• BP6: Variant 17-82616656-A-G is Benign according to our data. Variant chr17-82616656-A-G is described in ClinVar as [Benign]. Clinvar id is 1684228.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR45B	NM_019613.4	c.807-11T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000392325.9
WDR45B	XM_005256377.6	c.705-11T>C		splice_polypyrimidine_tract_variant, intron_variant
WDR45B	XM_047436412.1	c.651-11T>C		splice_polypyrimidine_tract_variant, intron_variant
WDR45B	XM_047436413.1	c.453-11T>C		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR45B	ENST00000392325.9	c.807-11T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_019613.4	P1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31487 AN: 152096 Hom.: 3629 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.224

GnomAD3 exomes AF: 0.236 AC: 59394 AN: 251342 Hom.: 7406 AF XY: 0.238 AC XY: 32364 AN XY: 135874

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.282

Gnomad ASJ exome AF: 0.251

Gnomad EAS exome AF: 0.150

Gnomad SAS exome AF: 0.238

Gnomad FIN exome AF: 0.254

Gnomad NFE exome AF: 0.250

Gnomad OTH exome AF: 0.244

GnomAD4 exome AF: 0.248 AC: 362243 AN: 1461576 Hom.: 45855 Cov.: 37 AF XY: 0.248 AC XY: 180252 AN XY: 727058

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.279

Gnomad4 ASJ exome AF: 0.245

Gnomad4 EAS exome AF: 0.148

Gnomad4 SAS exome AF: 0.242

Gnomad4 FIN exome AF: 0.255

Gnomad4 NFE exome AF: 0.255

Gnomad4 OTH exome AF: 0.237

GnomAD4 genome AF: 0.207 AC: 31488 AN: 152214 Hom.: 3628 Cov.: 33 AF XY: 0.209 AC XY: 15546 AN XY: 74416

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.221

Alfa AF: 0.220 Hom.: 1427

Bravo AF: 0.205

Asia WGS AF: 0.181 AC: 628 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	12
Dann	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000063
dbscSNV1_RF	Benign	0.034
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: rs12950772; hg19: chr17-80574532; COSMIC: COSV66408334; COSMIC: COSV66408334;