rs56282400

Variant names:

• chr5-6599876-A-C
• rs56282400
• NM_017755.6:c.*50T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-6599876-A-C
• chr5-6599876-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_017755.6(NSUN2):​c.*50T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0184 in 1,551,342 control chromosomes in the GnomAD database, including 338 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (26 hom., cov: 33)
  • Exomes 𝑓: 0.019 (312 hom.)
• Consequence: NSUN2 NM_017755.6 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.289
• Publications: 4 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]

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 5-6599876-A-C is Benign according to our data. Variant chr5-6599876-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 354044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0132 (2015/152334) while in subpopulation NFE AF = 0.0212 (1441/68020). AF 95% confidence interval is 0.0203. There are 26 homozygotes in GnomAd4. There are 924 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSUN2	NM_017755.6	MANE Select	c.*50T>G		3_prime_UTR	Exon 19 of 19	NP_060225.4
	NSUN2	NM_001193455.2		c.*50T>G		3_prime_UTR	Exon 18 of 18	NP_001180384.1	Q08J23-2
	NSUN2	NR_037947.2		n.2334T>G		non_coding_transcript_exon	Exon 18 of 18

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSUN2	ENST00000264670.11	TSL:1 MANE Select	c.*50T>G		3_prime_UTR	Exon 19 of 19	ENSP00000264670.6	Q08J23-1
	NSUN2	ENST00000505892.5	TSL:1	n.2923T>G		non_coding_transcript_exon	Exon 13 of 13
	NSUN2	ENST00000902915.1		c.*50T>G		3_prime_UTR	Exon 20 of 20	ENSP00000572974.1

Frequencies

GnomAD3 genomes AF: 0.0133 AC: 2017 AN: 152216 Hom.: 26 Cov.: 33

Gnomad AFR AF: 0.00475

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0175

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.00169

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0212

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.0129 AC: 3009 AN: 233670 AF XY: 0.0131

Gnomad AFR exome AF: 0.00425

Gnomad AMR exome AF: 0.0115

Gnomad ASJ exome AF: 0.00361

Gnomad EAS exome AF: 0.0000553

Gnomad FIN exome AF: 0.00244

Gnomad NFE exome AF: 0.0210

Gnomad OTH exome AF: 0.0138

GnomAD4 exome AF: 0.0190 AC: 26516 AN: 1399008 Hom.: 312 Cov.: 25 AF XY: 0.0186 AC XY: 12930 AN XY: 695556

African (AFR) AF: 0.00280 AC: 90 AN: 32184

American (AMR) AF: 0.0125 AC: 531 AN: 42608

Ashkenazi Jewish (ASJ) AF: 0.00334 AC: 82 AN: 24524

East Asian (EAS) AF: 0.0000763 AC: 3 AN: 39308

South Asian (SAS) AF: 0.00442 AC: 364 AN: 82408

European-Finnish (FIN) AF: 0.00419 AC: 196 AN: 46746

Middle Eastern (MID) AF: 0.0163 AC: 65 AN: 3984

European-Non Finnish (NFE) AF: 0.0228 AC: 24328 AN: 1069132

Other (OTH) AF: 0.0147 AC: 857 AN: 58114

GnomAD4 genome AF: 0.0132 AC: 2015 AN: 152334 Hom.: 26 Cov.: 33 AF XY: 0.0124 AC XY: 924 AN XY: 74484

African (AFR) AF: 0.00474 AC: 197 AN: 41578

American (AMR) AF: 0.0174 AC: 267 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00476 AC: 23 AN: 4832

European-Finnish (FIN) AF: 0.00169 AC: 18 AN: 10624

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0212 AC: 1441 AN: 68020

Other (OTH) AF: 0.0156 AC: 33 AN: 2114

Alfa AF: 0.00634 Hom.: 3

Bravo AF: 0.0147

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Intellectual disability, autosomal recessive 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.34
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism

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: rs56282400; hg19: chr5-6599989;