chr1-173824697-G-T

Variant names:

• chr1-173824697-G-T
• rs533128814
• NM_018122.5:c.-533G>T

Variant summary

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

The NM_018122.5(DARS2):​c.-533G>T variant causes a 5 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: DARS2 NM_018122.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.684
• Publications: 0 publications found

Genes affected

DARS2 (HGNC:25538): (aspartyl-tRNA synthetase 2, mitochondrial) The protein encoded by this gene belongs to the class-II aminoacyl-tRNA synthetase family. It is a mitochondrial enzyme that specifically aminoacylates aspartyl-tRNA. Mutations in this gene are associated with leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL). [provided by RefSeq, Nov 2009]

CENPL (HGNC:17879): (centromere protein L) CENPL is a subunit of a CENPH (MIM 605607)-CENPI (MIM 300065)-associated centromeric complex that targets CENPA (MIM 117139) to centromeres and is required for proper kinetochore function and mitotic progression (Okada et al., 2006) [PubMed 16622420].[supplied by OMIM, Mar 2008]

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=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DARS2	NM_018122.5	c.-533G>T		5_prime_UTR_variant	Exon 1 of 17	ENST00000649689.2	NP_060592.2
CENPL	NM_001387287.1	c.-587C>A		5_prime_UTR_variant	Exon 1 of 6	ENST00000682279.1	NP_001374216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DARS2	ENST00000649689.2	c.-533G>T		5_prime_UTR_variant	Exon 1 of 17		NM_018122.5	ENSP00000497569.1
CENPL	ENST00000682279.1	c.-587C>A		5_prime_UTR_variant	Exon 1 of 6		NM_001387287.1	ENSP00000507473.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 12892 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 7026

African (AFR) AF: 0.00 AC: 0 AN: 198

American (AMR) AF: 0.00 AC: 0 AN: 1584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 132

East Asian (EAS) AF: 0.00 AC: 0 AN: 576

South Asian (SAS) AF: 0.00 AC: 0 AN: 2584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 42

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6816

Other (OTH) AF: 0.00 AC: 0 AN: 632

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.5
DANN	Benign	0.62
PhyloP100		-0.68
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs533128814; hg19: chr1-173793835;