rs8192120

Variant names:

• chr5-6632207-C-A
• rs8192120
• NM_017755.6:c.255-230G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-6632207-C-A
• chr5-6632207-C-G
• chr5-6632207-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017755.6(NSUN2):​c.255-230G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,462 control chromosomes in the GnomAD database, including 15,964 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.45 (15964 hom., cov: 32)
• Consequence: NSUN2 NM_017755.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0230
• Publications: 7 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 5-6632207-C-A is Benign according to our data. Variant chr5-6632207-C-A is described in ClinVar as Benign. ClinVar VariationId is 1230653.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSUN2	NM_017755.6	c.255-230G>T		intron_variant	Intron 2 of 18	ENST00000264670.11	NP_060225.4
NSUN2	NM_001193455.2	c.254+392G>T		intron_variant	Intron 2 of 17		NP_001180384.1
NSUN2	NR_037947.2	n.320-230G>T		intron_variant	Intron 2 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSUN2	ENST00000264670.11	c.255-230G>T		intron_variant	Intron 2 of 18	1	NM_017755.6	ENSP00000264670.6
NSUN2	ENST00000506139.5	c.254+392G>T		intron_variant	Intron 2 of 17	2		ENSP00000420957.1
NSUN2	ENST00000504374.5	n.255-230G>T		intron_variant	Intron 2 of 17	2		ENSP00000421783.1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67587 AN: 151344 Hom.: 15960 Cov.: 32

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.446 AC: 67623 AN: 151462 Hom.: 15964 Cov.: 32 AF XY: 0.452 AC XY: 33419 AN XY: 73946

African (AFR) AF: 0.566 AC: 23341 AN: 41258

American (AMR) AF: 0.386 AC: 5878 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1059 AN: 3466

East Asian (EAS) AF: 0.735 AC: 3760 AN: 5118

South Asian (SAS) AF: 0.591 AC: 2838 AN: 4804

European-Finnish (FIN) AF: 0.444 AC: 4643 AN: 10460

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.367 AC: 24862 AN: 67822

Other (OTH) AF: 0.407 AC: 854 AN: 2098

Alfa AF: 0.380 Hom.: 14526

Bravo AF: 0.443

Asia WGS AF: 0.649 AC: 2256 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.46
PhyloP100		-0.023
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: rs8192120; hg19: chr5-6632320; COSMIC: COSV52957380; COSMIC: COSV52957380;