rs518673

Positions:

• chr5-6629817-G-A

Variant summary

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

The ENST00000264670.11(NSUN2):​c.359+2056C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 151,962 control chromosomes in the GnomAD database, including 9,025 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 0.34 (9025 hom., cov: 32)
• Consequence: NSUN2 ENST00000264670.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

Genes affected

NSUN2 (HGNC:25994): (NOP2/Sun RNA methyltransferase 2) This gene encodes a methyltransferase that catalyzes the methylation of cytosine to 5-methylcytosine (m5C) at position 34 of intron-containing tRNA(Leu)(CAA) precursors. This modification is necessary to stabilize the anticodon-codon pairing and correctly translate the mRNA. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSUN2	NM_017755.6	c.359+2056C>T		intron_variant		ENST00000264670.11	NP_060225.4
NSUN2	NM_001193455.2	c.254+2782C>T		intron_variant			NP_001180384.1
NSUN2	NR_037947.2	n.424+2056C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSUN2	ENST00000264670.11	c.359+2056C>T		intron_variant		1	NM_017755.6	ENSP00000264670	P2
NSUN2	ENST00000506139.5	c.254+2782C>T		intron_variant		2		ENSP00000420957	A2
NSUN2	ENST00000504374.5	c.359+2056C>T		intron_variant, NMD_transcript_variant		2		ENSP00000421783

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51448 AN: 151842 Hom.: 9022 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.339 AC: 51475 AN: 151962 Hom.: 9025 Cov.: 32 AF XY: 0.343 AC XY: 25461 AN XY: 74296

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.325

Alfa AF: 0.339 Hom.: 18173

Bravo AF: 0.337

Asia WGS AF: 0.318 AC: 1106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.52

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: rs518673; hg19: chr5-6629930;