chr5-6629817-G-A

Variant names:

• chr5-6629817-G-A
• rs518673
• NM_017755.6:c.359+2056C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017755.6(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 NM_017755.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 13 publications found

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]

NSUN2 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 5

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Dubowitz syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• RASopathy

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017755.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSUN2	NM_017755.6	MANE Select	c.359+2056C>T		intron	N/A	NP_060225.4
	NSUN2	NM_001193455.2		c.254+2782C>T		intron	N/A	NP_001180384.1
	NSUN2	NR_037947.2		n.424+2056C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSUN2	ENST00000264670.11	TSL:1 MANE Select	c.359+2056C>T		intron	N/A	ENSP00000264670.6
	NSUN2	ENST00000506139.5	TSL:2	c.254+2782C>T		intron	N/A	ENSP00000420957.1
	NSUN2	ENST00000504374.5	TSL:2	n.359+2056C>T		intron	N/A	ENSP00000421783.1

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

African (AFR) AF: 0.294 AC: 12179 AN: 41450

American (AMR) AF: 0.421 AC: 6424 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1117 AN: 3462

East Asian (EAS) AF: 0.261 AC: 1345 AN: 5154

South Asian (SAS) AF: 0.281 AC: 1354 AN: 4812

European-Finnish (FIN) AF: 0.448 AC: 4726 AN: 10552

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23099 AN: 67956

Other (OTH) AF: 0.325 AC: 684 AN: 2106

Alfa AF: 0.339 Hom.: 37167

Bravo AF: 0.337

Asia WGS AF: 0.318 AC: 1106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.52
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

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: rs518673; hg19: chr5-6629930;