rs2273802

Positions:

• chr14-100376562-G-A

Variant summary

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

The ENST00000335290.10(WDR25):​c.-158G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 1,231,630 control chromosomes in the GnomAD database, including 47,085 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 0.33 (9165 hom., cov: 34)
  • Exomes 𝑓: 0.26 (37920 hom.)
• Consequence: WDR25 ENST00000335290.10 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08

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]

WARS1 (HGNC:12729): (tryptophanyl-tRNA synthetase 1) Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAs, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. Two forms of tryptophanyl-tRNA synthetase exist, a cytoplasmic form, named WARS, and a mitochondrial form, named WARS2. Tryptophanyl-tRNA synthetase (WARS) catalyzes the aminoacylation of tRNA(trp) with tryptophan and is induced by interferon. Tryptophanyl-tRNA synthetase belongs to the class I tRNA synthetase family. Four transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR25	NM_001161476.3	c.-16+67G>A		intron_variant		ENST00000402312.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR25	ENST00000402312.8	c.-16+67G>A		intron_variant		2	NM_001161476.3	P1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50505 AN: 152054 Hom.: 9154 Cov.: 34

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.344

GnomAD4 exome AF: 0.256 AC: 276210 AN: 1079458 Hom.: 37920 Cov.: 35 AF XY: 0.255 AC XY: 129862 AN XY: 509574

Gnomad4 AFR exome AF: 0.400

Gnomad4 AMR exome AF: 0.515

Gnomad4 ASJ exome AF: 0.319

Gnomad4 EAS exome AF: 0.575

Gnomad4 SAS exome AF: 0.128

Gnomad4 FIN exome AF: 0.357

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.277

GnomAD4 genome AF: 0.332 AC: 50552 AN: 152172 Hom.: 9165 Cov.: 34 AF XY: 0.339 AC XY: 25211 AN XY: 74412

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.345

Alfa AF: 0.291 Hom.: 1108

Bravo AF: 0.353

Asia WGS AF: 0.359 AC: 1246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.92
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: rs2273802; hg19: chr14-100842899;