Variant 5-6599827-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017755.6(NSUN2):c.*99G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,032,074 control chromosomes in the GnomAD database, including 9,834 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1339 hom., cov: 33)

Exomes 𝑓: 0.13 ( 8495 hom. )

Consequence

NSUN2
NM_017755.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0880

Variant links:

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 links:

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

LINC01018 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 5-6599827-C-T is Benign according to our data. Variant chr5-6599827-C-T is described in ClinVar as [Benign]. Clinvar id is 354043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
NSUN2	NM_017755.6 linkuse as main transcript	c.*99G>A	3_prime_UTR_variant	19/19	ENST00000264670.11	NP_060225.4
NSUN2	NM_001193455.2 linkuse as main transcript	c.*99G>A	3_prime_UTR_variant	18/18		NP_001180384.1
NSUN2	NR_037947.2 linkuse as main transcript	n.2383G>A	non_coding_transcript_exon_variant	18/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSUN2	ENST00000264670.11 linkuse as main transcript	c.*99G>A		3_prime_UTR_variant	19/19	1	NM_017755.6	ENSP00000264670	P2	Q08J23-1
LINC01018	ENST00000661215.1 linkuse as main transcript	n.757-294C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17582

AN:

152176

Hom.:

1338

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0404

Gnomad AMI

AF:

0.132

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.0660

Gnomad EAS

AF:

0.248

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.101

GnomAD4 exome

AF:

0.128

AC:

112602

AN:

879780

Hom.:

8495

Cov.:

AF XY:

0.128

AC XY:

57958

AN XY:

451638

show subpopulations

Gnomad4 AFR exome

AF:

0.0358

Gnomad4 AMR exome

AF:

0.225

Gnomad4 ASJ exome

AF:

0.0634

Gnomad4 EAS exome

AF:

0.249

Gnomad4 SAS exome

AF:

0.166

Gnomad4 FIN exome

AF:

0.213

Gnomad4 NFE exome

AF:

0.112

Gnomad4 OTH exome

AF:

0.123

GnomAD4 genome

AF:

0.115

AC:

17586

AN:

152294

Hom.:

1339

Cov.:

AF XY:

0.124

AC XY:

9201

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0406

Gnomad4 AMR

AF:

0.181

Gnomad4 ASJ

AF:

0.0660

Gnomad4 EAS

AF:

0.248

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.231

Gnomad4 NFE

AF:

0.118

Gnomad4 OTH

AF:

0.0993

Alfa

AF:

0.113

Hom.:

983

Bravo

AF:

0.110

Asia WGS

AF:

0.238

AC:

828

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Intellectual disability, autosomal recessive 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.9

DANN

Benign

0.36

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over