17-82616012-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_019613.4(WDR45B):c.942C>T(p.Asp314=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00741 in 1,613,774 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0059 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0076 (65 hom.)
• Consequence: WDR45B NM_019613.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.868

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 17-82616012-G-A is Benign according to our data. Variant chr17-82616012-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 774726.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.868 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR45B	NM_019613.4	c.942C>T	p.Asp314=	synonymous_variant	10/10	ENST00000392325.9
WDR45B	XM_005256377.6	c.840C>T	p.Asp280=	synonymous_variant	9/9
WDR45B	XM_047436412.1	c.786C>T	p.Asp262=	synonymous_variant	8/8
WDR45B	XM_047436413.1	c.588C>T	p.Asp196=	synonymous_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR45B	ENST00000392325.9	c.942C>T	p.Asp314=	synonymous_variant	10/10	1	NM_019613.4	P1

Frequencies

GnomAD3 genomes AF: 0.00591 AC: 899 AN: 152040 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00193

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.00663

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00557

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00912

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00572 AC: 1436 AN: 251154 Hom.: 10 AF XY: 0.00583 AC XY: 792 AN XY: 135782

Gnomad AFR exome AF: 0.00222

Gnomad AMR exome AF: 0.00483

Gnomad ASJ exome AF: 0.00308

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00203

Gnomad FIN exome AF: 0.00497

Gnomad NFE exome AF: 0.00877

Gnomad OTH exome AF: 0.00603

GnomAD4 exome AF: 0.00757 AC: 11061 AN: 1461618 Hom.: 65 Cov.: 31 AF XY: 0.00728 AC XY: 5297 AN XY: 727130

Gnomad4 AFR exome AF: 0.00185

Gnomad4 AMR exome AF: 0.00519

Gnomad4 ASJ exome AF: 0.00390

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00165

Gnomad4 FIN exome AF: 0.00502

Gnomad4 NFE exome AF: 0.00883

Gnomad4 OTH exome AF: 0.00707

GnomAD4 genome AF: 0.00591 AC: 899 AN: 152156 Hom.: 0 Cov.: 31 AF XY: 0.00554 AC XY: 412 AN XY: 74382

Gnomad4 AFR AF: 0.00193

Gnomad4 AMR AF: 0.00662

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00557

Gnomad4 NFE AF: 0.00912

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00744 Hom.: 6

Bravo AF: 0.00568

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00905

EpiControl AF: 0.00984

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	WDR45B: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

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

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 27, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	7.4
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs147083174; hg19: chr17-80573888;