rs2273804

Variant names:

• chr14-100376300-C-A
• rs2273804
• ENST00000355338.6:c.-114G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-100376300-C-A
• chr14-100376300-C-G
• chr14-100376300-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000355338.6(WARS1):​c.-114G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000457 in 876,050 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: WARS1 ENST00000355338.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• Publications: 0 publications found

Genes affected

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]

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR25	NM_001161476.3	c.-211C>A		upstream_gene_variant		ENST00000402312.8	NP_001154948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR25	ENST00000402312.8	c.-211C>A		upstream_gene_variant		2	NM_001161476.3	ENSP00000385540.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000457 AC: 4 AN: 876050 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 417924

African (AFR) AF: 0.00 AC: 0 AN: 19438

American (AMR) AF: 0.00 AC: 0 AN: 7864

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12892

East Asian (EAS) AF: 0.00 AC: 0 AN: 25086

South Asian (SAS) AF: 0.00 AC: 0 AN: 14674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2512

European-Non Finnish (NFE) AF: 0.00000543 AC: 4 AN: 736442

Other (OTH) AF: 0.00 AC: 0 AN: 36836

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.18
DANN	Benign	0.28
PhyloP100		-2.2
PromoterAI		0.076	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2273804; hg19: chr14-100842637;