rs782179321

Positions:

• chrX-49074920-AG-A
• chrX-49074920-AG-AGG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001029896.2(WDR45):​c.974-9delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,180,848 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 0.000023 (0 hom. 6 hem.)
• Consequence: WDR45 NM_001029896.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.210

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]

ENSG00000288053 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant X-49074920-AG-A is Benign according to our data. Variant chrX-49074920-AG-A is described in ClinVar as [Benign]. Clinvar id is 473123.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0000234 (25/1069167) while in subpopulation MID AF= 0.000247 (1/4054). AF 95% confidence interval is 0.0000935. There are 0 homozygotes in gnomad4_exome. There are 6 alleles in male gnomad4_exome subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAdExome4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR45	NM_001029896.2	c.974-9delC		intron_variant		ENST00000376372.9	NP_001025067.1
WDR45	NM_007075.4	c.977-9delC		intron_variant			NP_009006.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR45	ENST00000376372.9	c.974-9delC		intron_variant		1	NM_001029896.2	ENSP00000365551.3
ENSG00000288053	ENST00000376358.4	c.521+443delC		intron_variant		2		ENSP00000365536.3

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 111681 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 33929

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000944

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000189

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000234 AC: 25 AN: 1069167 Hom.: 0 Cov.: 28 AF XY: 0.0000177 AC XY: 6 AN XY: 338585

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000199

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000749

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000159

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000179 AC: 2 AN: 111681 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 33929

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000944

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000189

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000189

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neurodegeneration with brain iron accumulation 5 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 13, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs782179321; hg19: chrX-48932579;