1-224393979-T-C

Position:

• chr1-224393979-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001379403.1(WDR26):​c.2109A>G​(p.Glu703Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,536,420 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0064 (10 hom., cov: 32)
  • Exomes 𝑓: 0.00056 (8 hom.)
• Consequence: WDR26 NM_001379403.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.508

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 1-224393979-T-C is Benign according to our data. Variant chr1-224393979-T-C is described in ClinVar as [Benign]. Clinvar id is 767752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.508 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00638 (971/152308) while in subpopulation AFR AF= 0.0219 (912/41572). AF 95% confidence interval is 0.0208. There are 10 homozygotes in gnomad4. There are 420 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 971 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR26	NM_001379403.1	c.2109A>G	p.Glu703Glu	synonymous_variant	13/14	ENST00000414423.9	NP_001366332.1
WDR26	NM_025160.7	c.1809A>G	p.Glu603Glu	synonymous_variant	13/14		NP_079436.4
WDR26	NM_001115113.3	c.1761A>G	p.Glu587Glu	synonymous_variant	13/14		NP_001108585.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR26	ENST00000414423.9	c.2109A>G	p.Glu703Glu	synonymous_variant	13/14	1	NM_001379403.1	ENSP00000408108.4

Frequencies

GnomAD3 genomes AF: 0.00636 AC: 968 AN: 152190 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0219

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00527

GnomAD3 exomes AF: 0.00166 AC: 411 AN: 247366 Hom.: 6 AF XY: 0.00111 AC XY: 149 AN XY: 133762

Gnomad AFR exome AF: 0.0219

Gnomad AMR exome AF: 0.00150

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000670

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000356

Gnomad OTH exome AF: 0.000333

GnomAD4 exome AF: 0.000560 AC: 775 AN: 1384112 Hom.: 8 Cov.: 30 AF XY: 0.000465 AC XY: 317 AN XY: 681648

Gnomad4 AFR exome AF: 0.0184

Gnomad4 AMR exome AF: 0.00152

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000384

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000360

Gnomad4 OTH exome AF: 0.00116

GnomAD4 genome AF: 0.00638 AC: 971 AN: 152308 Hom.: 10 Cov.: 32 AF XY: 0.00564 AC XY: 420 AN XY: 74478

Gnomad4 AFR AF: 0.0219

Gnomad4 AMR AF: 0.00261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00522

Alfa AF: 0.00266 Hom.: 1

Bravo AF: 0.00688

Asia WGS AF: 0.00144 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.8
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs35958886; hg19: chr1-224581681;