1-224404566-GTA-G

Variant names:

• chr1-224404566-GTA-G
• rs1553354980
• NM_001379403.1:c.1461_1462delTA

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001379403.1(WDR26):​c.1461_1462delTA​(p.His489ProfsTer6) variant causes a frameshift, splice region change. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR26 NM_001379403.1 frameshift, splice_region
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.98
• 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]

WDR26 Gene-Disease associations (from GenCC):

• Skraban-Deardorff syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Illumina, ClinGen

ACMG classification

Our verdict: Pathogenic. The variant received 11 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 1-224404566-GTA-G is Pathogenic according to our data. Variant chr1-224404566-GTA-G is described in ClinVar as Pathogenic. ClinVar VariationId is 433007.Status of the report is no_assertion_criteria_provided, 0 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR26	NM_001379403.1	MANE Select	c.1461_1462delTA	p.His489ProfsTer6	frameshift splice_region	Exon 8 of 14	NP_001366332.1
	WDR26	NM_025160.7		c.1161_1162delTA	p.His389ProfsTer6	frameshift splice_region	Exon 8 of 14	NP_079436.4
	WDR26	NM_001115113.3		c.1113_1114delTA	p.His373ProfsTer6	frameshift splice_region	Exon 8 of 14	NP_001108585.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR26	ENST00000414423.9	TSL:1 MANE Select	c.1461_1462delTA	p.His489ProfsTer6	frameshift splice_region	Exon 8 of 14	ENSP00000408108.4
	WDR26	ENST00000443112.7	TSL:1	n.2791_2792delTA		splice_region non_coding_transcript_exon	Exon 8 of 15
	WDR26	ENST00000486652.5	TSL:1	n.*610_*611delTA		splice_region non_coding_transcript_exon	Exon 9 of 16	ENSP00000422758.1

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

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Skraban-Deardorff syndrome Pathogenic:1

Aug 15, 2017

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.0
Mutation Taster		=3/197	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs1553354980; hg19: chr1-224592268;