1-224398256-A-C

Position:

• chr1-224398256-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001379403.1(WDR26):​c.1945-30T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,597,406 control chromosomes in the GnomAD database, including 42,686 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (7203 hom., cov: 32)
  • Exomes 𝑓: 0.21 (35483 hom.)
• Consequence: WDR26 NM_001379403.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.220

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-224398256-A-C is Benign according to our data. Variant chr1-224398256-A-C is described in ClinVar as [Benign]. Clinvar id is 1684226.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR26	NM_001379403.1	c.1945-30T>G		intron_variant		ENST00000414423.9	NP_001366332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR26	ENST00000414423.9	c.1945-30T>G		intron_variant		1	NM_001379403.1	ENSP00000408108.4

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42234 AN: 151988 Hom.: 7191 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.00654

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.276

GnomAD3 exomes AF: 0.206 AC: 48351 AN: 234998 Hom.: 6239 AF XY: 0.203 AC XY: 25820 AN XY: 127272

Gnomad AFR exome AF: 0.483

Gnomad AMR exome AF: 0.128

Gnomad ASJ exome AF: 0.250

Gnomad EAS exome AF: 0.00327

Gnomad SAS exome AF: 0.122

Gnomad FIN exome AF: 0.224

Gnomad NFE exome AF: 0.232

Gnomad OTH exome AF: 0.222

GnomAD4 exome AF: 0.212 AC: 305931 AN: 1445300 Hom.: 35483 Cov.: 32 AF XY: 0.210 AC XY: 150758 AN XY: 718668

Gnomad4 AFR exome AF: 0.483

Gnomad4 AMR exome AF: 0.133

Gnomad4 ASJ exome AF: 0.244

Gnomad4 EAS exome AF: 0.00157

Gnomad4 SAS exome AF: 0.122

Gnomad4 FIN exome AF: 0.227

Gnomad4 NFE exome AF: 0.218

Gnomad4 OTH exome AF: 0.224

GnomAD4 genome AF: 0.278 AC: 42280 AN: 152106 Hom.: 7203 Cov.: 32 AF XY: 0.273 AC XY: 20300 AN XY: 74364

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.00636

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.271

Alfa AF: 0.259 Hom.: 1273

Bravo AF: 0.283

Asia WGS AF: 0.0980 AC: 340 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Skraban-Deardorff syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.4
DANN	Benign	0.75

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: rs7522956; hg19: chr1-224585958;