chr14-100416068-A-G

Position:

• chr14-100416068-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001161476.3(WDR25):​c.822+34322A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,096 control chromosomes in the GnomAD database, including 5,543 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5543 hom., cov: 32)
• Consequence: WDR25 NM_001161476.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226

Genes affected

WDR25 (HGNC:21064): (WD repeat domain 25) This gene encodes a protein containing 7 WD repeats. WD repeats are approximately 30 to 40-amino acid domains containing several conserved residues, typically having a Tryptophan-Aspartic acid dipeptide (WD) at the C-terminal end. WD domains are involved in protein-protein interactions in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR25	NM_001161476.3	c.822+34322A>G		intron_variant		ENST00000402312.8	NP_001154948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR25	ENST00000402312.8	c.822+34322A>G		intron_variant		2	NM_001161476.3	ENSP00000385540	P1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37576 AN: 151978 Hom.: 5539 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.296

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.247 AC: 37582 AN: 152096 Hom.: 5543 Cov.: 32 AF XY: 0.255 AC XY: 18970 AN XY: 74316

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.299

Alfa AF: 0.240 Hom.: 598

Bravo AF: 0.258

Asia WGS AF: 0.346 AC: 1203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.85

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: rs10144321; hg19: chr14-100882405;