rs1553350638

Variant names:

• chr1-224389854-C-A
• rs1553350638
• NM_001379403.1:c.2267G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001379403.1(WDR26):​c.2267G>T​(p.Cys756Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000868 in 115,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000087 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WDR26 NM_001379403.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.52
• 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, ClinGen, Illumina, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4013627).

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.2267G>T	p.Cys756Phe	missense	Exon 14 of 14	NP_001366332.1	A0A499FIZ0
	WDR26	NM_025160.7		c.1967G>T	p.Cys656Phe	missense	Exon 14 of 14	NP_079436.4
	WDR26	NM_001115113.3		c.1919G>T	p.Cys640Phe	missense	Exon 14 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.2267G>T	p.Cys756Phe	missense	Exon 14 of 14	ENSP00000408108.4	A0A499FIZ0
	WDR26	ENST00000443112.7	TSL:1	n.3757G>T		non_coding_transcript_exon	Exon 15 of 15
	WDR26	ENST00000486652.5	TSL:1	n.*1522G>T		non_coding_transcript_exon	Exon 16 of 16	ENSP00000422758.1	H0Y917

Frequencies

GnomAD3 genomes AF: 0.00000868 AC: 1 AN: 115224 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000126

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1147278 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 570150

African (AFR) AF: 0.00 AC: 0 AN: 21906

American (AMR) AF: 0.00 AC: 0 AN: 28086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15776

East Asian (EAS) AF: 0.00 AC: 0 AN: 13174

South Asian (SAS) AF: 0.00 AC: 0 AN: 77520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4338

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 914340

Other (OTH) AF: 0.00 AC: 0 AN: 41530

GnomAD4 genome AF: 0.00000868 AC: 1 AN: 115224 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 52398

African (AFR) AF: 0.00 AC: 0 AN: 29638

American (AMR) AF: 0.000126 AC: 1 AN: 7914

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3254

East Asian (EAS) AF: 0.00 AC: 0 AN: 3308

South Asian (SAS) AF: 0.00 AC: 0 AN: 3256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 136

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 61602

Other (OTH) AF: 0.00 AC: 0 AN: 1542

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

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
AlphaMissense	Benign	0.19
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.3	L
PhyloP100		5.5
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0010	D
Vest4		0.57
MutPred		0.24		Gain of glycosylation at S657 (P = 0.0836)
MVP		0.51
MPC		2.0
ClinPred		0.88	D
GERP RS		5.2
Varity_R		0.65
Mutation Taster		=12/88	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1553350638; hg19: chr1-224577556;