5-6599109-A-G

Variant names:

• chr5-6599109-A-G
• rs6876835
• ENST00000661215.2:n.775-1012A>G

Variant summary

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

The ENST00000661215.2(LINC01018):​n.775-1012A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,068 control chromosomes in the GnomAD database, including 15,627 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 0.45 (15624 hom., cov: 33)
  • Exomes 𝑓: 0.64 (3 hom.)
• Consequence: LINC01018 ENST00000661215.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 13 publications found

Genes affected

LINC01018 (HGNC:27394): (long intergenic non-protein coding RNA 1018)

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000661215.2. 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.*817T>C		downstream_gene	N/A	NP_060225.4
	NSUN2	NM_001193455.2		c.*817T>C		downstream_gene	N/A	NP_001180384.1
	NSUN2	NR_037947.2		n.*130T>C		downstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC01018	ENST00000661215.2		n.775-1012A>G		intron	N/A
	LINC01018	ENST00000669289.1		n.571-1012A>G		intron	N/A
	LINC01018	ENST00000752507.1		n.719+13082A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68169 AN: 151936 Hom.: 15629 Cov.: 33

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.409

GnomAD4 exome AF: 0.643 AC: 9 AN: 14 Hom.: 3 AF XY: 0.600 AC XY: 6 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 6 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 3 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.448 AC: 68191 AN: 152054 Hom.: 15624 Cov.: 33 AF XY: 0.456 AC XY: 33899 AN XY: 74322

African (AFR) AF: 0.419 AC: 17377 AN: 41458

American (AMR) AF: 0.454 AC: 6943 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1272 AN: 3470

East Asian (EAS) AF: 0.666 AC: 3441 AN: 5164

South Asian (SAS) AF: 0.603 AC: 2909 AN: 4826

European-Finnish (FIN) AF: 0.505 AC: 5340 AN: 10570

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29567 AN: 67980

Other (OTH) AF: 0.408 AC: 858 AN: 2102

Alfa AF: 0.435 Hom.: 46892

Bravo AF: 0.440

Asia WGS AF: 0.631 AC: 2193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.036
DANN	Benign	0.55
PhyloP100		-1.8

Splicing

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

Other links and lift over

dbSNP: rs6876835; hg19: chr5-6599222;