Variant chr17-82616656-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.41

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 -20 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_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
WDR45B	NM_019613.4 linkuse as main transcript	c.807-11T>C	splice_polypyrimidine_tract_variant, intron_variant	ENST00000392325.9	NP_062559.2
WDR45B	XM_005256377.6 linkuse as main transcript	c.705-11T>C	splice_polypyrimidine_tract_variant, intron_variant		XP_005256434.1
WDR45B	XM_047436412.1 linkuse as main transcript	c.651-11T>C	splice_polypyrimidine_tract_variant, intron_variant		XP_047292368.1
WDR45B	XM_047436413.1 linkuse as main transcript	c.453-11T>C	splice_polypyrimidine_tract_variant, intron_variant		XP_047292369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR45B	ENST00000392325.9 linkuse as main transcript	c.807-11T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_019613.4	ENSP00000376139	P1

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31487

AN:

152096

Hom.:

3629

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.248

AC XY:

180252

AN XY:

727058

show subpopulations

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.:

AF XY:

0.209

AC XY:

15546

AN XY:

74416

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

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

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