NM_001379403.1:c.359G>A

Variant names:

• chr1-224434047-C-T
• rs796052210
• NM_001379403.1:c.359G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001379403.1(WDR26):​c.359G>A​(p.Gly120Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,454,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: WDR26 NM_001379403.1 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.30
• Publications: 2 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1573048).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

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.359G>A	p.Gly120Glu	missense	Exon 1 of 14	NP_001366332.1
	WDR26	NM_025160.7		c.59G>A	p.Gly20Glu	missense	Exon 1 of 14	NP_079436.4
	WDR26	NM_001115113.3		c.59G>A	p.Gly20Glu	missense	Exon 1 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.359G>A	p.Gly120Glu	missense	Exon 1 of 14	ENSP00000408108.4
	WDR26	ENST00000486652.5	TSL:1	n.35G>A		non_coding_transcript_exon	Exon 1 of 16	ENSP00000422758.1
	WDR26	ENST00000678555.1		c.359G>A	p.Gly120Glu	missense	Exon 1 of 13	ENSP00000504302.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152072 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

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

GnomAD2 exomes AF: 0.0000143 AC: 1 AN: 69886 AF XY: 0.0000272

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000121

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000461 AC: 6 AN: 1302158 Hom.: 0 Cov.: 59 AF XY: 0.00000631 AC XY: 4 AN XY: 634354

African (AFR) AF: 0.00 AC: 0 AN: 28998

American (AMR) AF: 0.00 AC: 0 AN: 22816

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19606

East Asian (EAS) AF: 0.000143 AC: 5 AN: 35060

South Asian (SAS) AF: 0.00 AC: 0 AN: 66956

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3812

European-Non Finnish (NFE) AF: 9.61e-7 AC: 1 AN: 1040530

Other (OTH) AF: 0.00 AC: 0 AN: 54144

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152072 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74286

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67976

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Long QT syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.092	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.78	T
M_CAP	Pathogenic	0.45	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.3
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	0.060	N
REVEL	Uncertain	0.35
Sift	Benign	0.34	T
Sift4G	Uncertain	0.0050	D
Vest4		0.35
MutPred		0.40		Gain of solvent accessibility (P = 0.0411)
MVP		0.22
MPC		1.3
ClinPred		0.19	T
GERP RS		2.6
PromoterAI		-0.079	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.12
Mutation Taster		=90/10	polymorphism

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: rs796052210; hg19: chr1-224621749; COSMIC: COSV104595340; COSMIC: COSV104595340;