rs112294032

Variant names:

• chr1-54757589-T-A
• rs112294032
• NM_152268.4:c.*145A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-54757589-T-A
• chr1-54757589-T-C

Variant summary

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

The NM_152268.4(PARS2):​c.*145A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PARS2 NM_152268.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• Publications: 1 publications found

Genes affected

PARS2 (HGNC:30563): (prolyl-tRNA synthetase 2, mitochondrial) This gene encodes a putative member of the class II family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. This protein is encoded by the nuclear genome but is likely to be imported to the mitochondrion where it is thought to catalyze the ligation of proline to tRNA molecules. Mutations have been found in this gene in some patients with Alpers syndrome. [provided by RefSeq, Mar 2015]

PARS2 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 75

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• mitochondrial disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152268.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARS2	NM_152268.4	MANE Select	c.*145A>T		3_prime_UTR	Exon 2 of 2	NP_689481.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARS2	ENST00000371279.4	TSL:1 MANE Select	c.*145A>T		3_prime_UTR	Exon 2 of 2	ENSP00000360327.3	Q7L3T8
	PARS2	ENST00000887740.1		c.*145A>T		3_prime_UTR	Exon 2 of 2	ENSP00000557799.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 437254 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 228452

African (AFR) AF: 0.00 AC: 0 AN: 12258

American (AMR) AF: 0.00 AC: 0 AN: 16680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13420

East Asian (EAS) AF: 0.00 AC: 0 AN: 30410

South Asian (SAS) AF: 0.00 AC: 0 AN: 40902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1946

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 266550

Other (OTH) AF: 0.00 AC: 0 AN: 25528

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 13

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.8
DANN	Benign	0.53
PhyloP100		0.063

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

Other links and lift over

dbSNP: rs112294032; hg19: chr1-55223262;