rs201384117

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001029896.2(WDR45):c.437-27A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000036 in 1,140,106 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 15 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.000037 ( 0 hom. 13 hem. )

Consequence

WDR45
NM_001029896.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.230

Publications

0 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 -8 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (MetaRNN=0.032790303).

BS2

High AC in GnomAdExome4 at 38 XL,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR45	NM_001029896.2 link	c.437-27A>T		intron_variant	Intron 6 of 10	ENST00000376372.9	NP_001025067.1	Q9Y484-1A0A024QYX1
WDR45	NM_007075.4 link	c.440-27A>T		intron_variant	Intron 7 of 11		NP_009006.2	Q9Y484-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR45	ENST00000376372.9 link	c.437-27A>T		intron_variant	Intron 6 of 10	1	NM_001029896.2	ENSP00000365551.3		Q9Y484-1
ENSG00000288053	ENST00000376358.4 link	c.131-27A>T		intron_variant	Intron 3 of 7	2		ENSP00000365536.3		A6NM71

Frequencies

GnomAD3 genomes

AF:

0.0000275

AC:

AN:

109261

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000173

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000191

Gnomad OTH

AF:

0.000680

GnomAD2 exomes

AF:

0.0000555

AC:

AN:

162303

AF XY:

0.0000588

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000407

Gnomad NFE exome

AF:

0.0000287

Gnomad OTH exome

AF:

0.000243

GnomAD4 exome

AF:

0.0000369

AC:

AN:

1030845

Hom.:

Cov.:

AF XY:

0.0000424

AC XY:

AN XY:

306383

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25123

American (AMR)

AF:

0.00

AC:

AN:

33812

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18791

East Asian (EAS)

AF:

0.00

AC:

AN:

29682

South Asian (SAS)

AF:

0.00

AC:

AN:

51350

European-Finnish (FIN)

AF:

0.000802

AC:

AN:

39878

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3852

European-Non Finnish (NFE)

AF:

0.00000637

AC:

AN:

784438

Other (OTH)

AF:

0.0000228

AC:

AN:

43919

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.541

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000275

AC:

AN:

109261

Hom.:

Cov.:

AF XY:

0.0000627

AC XY:

AN XY:

31903

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29948

American (AMR)

AF:

0.00

AC:

AN:

10199

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2622

East Asian (EAS)

AF:

0.00

AC:

AN:

3434

South Asian (SAS)

AF:

0.00

AC:

AN:

2556

European-Finnish (FIN)

AF:

0.000173

AC:

AN:

5777

Middle Eastern (MID)

AF:

0.00

AC:

AN:

233

European-Non Finnish (NFE)

AF:

0.0000191

AC:

AN:

52348

Other (OTH)

AF:

0.000680

AC:

AN:

1471

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.000198

Hom.:

ExAC

AF:

0.0000661

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.6

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.0020

.;.;T

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.17

T;T;T

M_CAP

Benign

0.0086

MetaRNN

Benign

0.033

T;T;T

MetaSVM

Benign

-1.0

PhyloP100

-0.23

PROVEAN

Benign

0.15

N;N;N

REVEL

Benign

0.011

Sift

Benign

0.65

T;T;T

Sift4G

Benign

0.75

T;.;.

Vest4

0.23

MutPred

0.40

Loss of ubiquitination at K145 (P = 0.0508);.;Loss of ubiquitination at K145 (P = 0.0508);

MVP

0.18

ClinPred

0.0071

GERP RS

-2.3

BranchPoint Hunter

1.0

PromoterAI

0.028

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over