rs1553353206

Variant names:

• chr1-224398524-TACATTTAACA-T
• rs1553353206
• NM_001379403.1:c.1925_1934delTGTTAAATGT

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001379403.1(WDR26):​c.1925_1934delTGTTAAATGT​(p.Leu642fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR26 NM_001379403.1 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 9.25
• Publications: 0 publications found

Genes affected

WDR26 (HGNC:21208): (WD repeat domain 26) 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. Two transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MIR4742 (HGNC:41565): (microRNA 4742) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-224398524-TACATTTAACA-T is Pathogenic according to our data. Variant chr1-224398524-TACATTTAACA-T is described in ClinVar as Pathogenic. ClinVar VariationId is 522095.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379403.1. 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
	WDR26	NM_001379403.1	MANE Select	c.1925_1934delTGTTAAATGT	p.Leu642fs	frameshift	Exon 11 of 14	NP_001366332.1	A0A499FIZ0
	WDR26	NM_025160.7		c.1625_1634delTGTTAAATGT	p.Leu542fs	frameshift	Exon 11 of 14	NP_079436.4
	WDR26	NM_001115113.3		c.1577_1586delTGTTAAATGT	p.Leu526fs	frameshift	Exon 11 of 14	NP_001108585.2	Q9H7D7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR26	ENST00000414423.9	TSL:1 MANE Select	c.1925_1934delTGTTAAATGT	p.Leu642fs	frameshift	Exon 11 of 14	ENSP00000408108.4	A0A499FIZ0
	WDR26	ENST00000443112.7	TSL:1	n.3255_3264delTGTTAAATGT		non_coding_transcript_exon	Exon 11 of 15
	WDR26	ENST00000486652.5	TSL:1	n.*1180_*1189delTGTTAAATGT		non_coding_transcript_exon	Exon 13 of 16	ENSP00000422758.1	H0Y917

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.2
Mutation Taster		=1/199	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs1553353206; hg19: chr1-224586226;