X-49075271-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001029896.2(WDR45):c.838G>A(p.Val280Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,209,412 control chromosomes in the GnomAD database, including 51 homozygotes. There are 829 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0067 ( 18 hom., 288 hem., cov: 24)

Exomes 𝑓: 0.0018 ( 33 hom. 541 hem. )

Consequence

WDR45
NM_001029896.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 7.26

Publications

5 publications found

Variant links:

Genes affected

WDR45 (HGNC:28912): (WD repeat domain 45) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene has a pseudogene at chromosome 4q31.3. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the biological validity and full-length nature of some variants have not been determined. [provided by RefSeq, Jul 2008]

WDR45 Gene-Disease associations (from GenCC):

neurodegeneration with brain iron accumulation 5
Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, G2P
X-linked complex neurodevelopmental disorder
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
infantile spasms
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

WDR45 links:

ENSG00000288053 (HGNC:):

ENSG00000288053 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005992919).

BP6

Variant X-49075271-C-T is Benign according to our data. Variant chrX-49075271-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 282969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0586 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001029896.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR45	NM_001029896.2	MANE Select	c.838G>A	p.Val280Met	missense	Exon 10 of 11	NP_001025067.1
	WDR45	NM_007075.4		c.841G>A	p.Val281Met	missense	Exon 11 of 12	NP_009006.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
WDR45	ENST00000376372.9	TSL:1 MANE Select	c.838G>A	p.Val280Met	missense	Exon 10 of 11	ENSP00000365551.3
WDR45	ENST00000356463.7	TSL:1	c.841G>A	p.Val281Met	missense	Exon 11 of 12	ENSP00000348848.3
WDR45	ENST00000376368.7	TSL:1	c.841G>A	p.Val281Met	missense	Exon 10 of 11	ENSP00000365546.2

Frequencies

GnomAD3 genomes

AF:

0.00672

AC:

755

AN:

112294

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0623

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00364

Gnomad SAS

AF:

0.000370

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000245

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.00670

AC:

1209

AN:

180428

AF XY:

0.00491

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.0394

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00414

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000112

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.00178

AC:

1957

AN:

1097065

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

541

AN XY:

362495

show subpopulations

African (AFR)

AF:

0.000872

AC:

AN:

26388

American (AMR)

AF:

0.0446

AC:

1565

AN:

35110

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19358

East Asian (EAS)

AF:

0.00282

AC:

AN:

30165

South Asian (SAS)

AF:

0.000500

AC:

AN:

54042

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40379

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.0000915

AC:

AN:

841460

Other (OTH)

AF:

0.00389

AC:

179

AN:

46031

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

191

286

382

477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00675

AC:

758

AN:

112347

Hom.:

Cov.:

AF XY:

0.00833

AC XY:

288

AN XY:

34559

show subpopulations

African (AFR)

AF:

0.00129

AC:

AN:

31015

American (AMR)

AF:

0.0625

AC:

668

AN:

10682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2650

East Asian (EAS)

AF:

0.00365

AC:

AN:

3561

South Asian (SAS)

AF:

0.000371

AC:

AN:

2698

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6167

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.000245

AC:

AN:

53154

Other (OTH)

AF:

0.0151

AC:

AN:

1521

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.0108

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.00349

AC:

424

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (3)

Inborn genetic diseases (1)

Neurodegeneration with brain iron accumulation 5 (1)

Neurodegeneration with brain iron accumulation 5;C3808786:Oculocutaneous albinism type 7 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.041

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.0060

MetaSVM

Benign

-0.88

MutationAssessor

Benign

-0.070

PhyloP100

7.3

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.50

REVEL

Uncertain

0.30

Sift

Benign

0.61

Sift4G

Benign

0.59

Polyphen

0.027

Vest4

0.28

MVP

0.60

MPC

0.62

ClinPred

0.021

GERP RS

4.1

PromoterAI

-0.030

Neutral

(source)

Varity_R

0.27

gMVP

0.49

Mutation Taster

=81/19

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over