Variant chr17-82616012-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.868

Variant links:

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]

WDR45B links:

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]

FOXK2 links:

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ACMG classification

Classification made for transcript

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 GnomAdExome4 at 65 AR gene

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR45B	ENST00000392325.9 linkuse as main transcript	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.:

Cov.:

show subpopulations

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.:

AF XY:

0.00583

AC XY:

792

AN XY:

135782

show subpopulations

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.:

Cov.:

AF XY:

0.00728

AC XY:

5297

AN XY:

727130

show subpopulations

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.:

Cov.:

AF XY:

0.00554

AC XY:

412

AN XY:

74382

show subpopulations

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.:

Bravo

AF:

0.00568

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00905

EpiControl

AF:

0.00984

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	WDR45B: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over