17-82644032-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_019613.4(WDR45B):c.68-9C>T 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 0.000705 in 1,613,986 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (8 hom., cov: 33)
  • Exomes 𝑓: 0.00039 (3 hom.)
• Consequence: WDR45B NM_019613.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00004750
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.834

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 17-82644032-G-A is Benign according to our data. Variant chr17-82644032-G-A is described in ClinVar as [Benign]. Clinvar id is 719573.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR45B	NM_019613.4	c.68-9C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000392325.9
WDR45B	XM_005256377.6	c.68-9C>T		splice_polypyrimidine_tract_variant, intron_variant
WDR45B	XM_047436414.1	c.68-9C>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR45B	ENST00000392325.9	c.68-9C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_019613.4	P1

Frequencies

GnomAD3 genomes AF: 0.00368 AC: 560 AN: 152178 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.000991 AC: 247 AN: 249248 Hom.: 0 AF XY: 0.000791 AC XY: 107 AN XY: 135264

Gnomad AFR exome AF: 0.0131

Gnomad AMR exome AF: 0.000551

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000885

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000395 AC: 577 AN: 1461690 Hom.: 3 Cov.: 31 AF XY: 0.000359 AC XY: 261 AN XY: 727140

Gnomad4 AFR exome AF: 0.0124

Gnomad4 AMR exome AF: 0.000671

Gnomad4 ASJ exome AF: 0.00122

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000288

Gnomad4 OTH exome AF: 0.00108

GnomAD4 genome AF: 0.00368 AC: 561 AN: 152296 Hom.: 8 Cov.: 33 AF XY: 0.00372 AC XY: 277 AN XY: 74468

Gnomad4 AFR AF: 0.0125

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00177 Hom.: 0

Bravo AF: 0.00412

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	9.6
Dann	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000048
dbscSNV1_RF	Benign	0.0
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: rs76260584; hg19: chr17-80601908;