rs375443052
Positions:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_017755.6(NSUN2):c.2271C>T(p.Gly757=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
NSUN2
NM_017755.6 synonymous
NM_017755.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0730
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 5-6599959-G-A is Benign according to our data. Variant chr5-6599959-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 436085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.073 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000092 (14/152252) while in subpopulation AFR AF= 0.000265 (11/41470). AF 95% confidence interval is 0.000149. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NSUN2 | NM_017755.6 | c.2271C>T | p.Gly757= | synonymous_variant | 19/19 | ENST00000264670.11 | |
NSUN2 | NM_001193455.2 | c.2166C>T | p.Gly722= | synonymous_variant | 18/18 | ||
NSUN2 | NR_037947.2 | n.2251C>T | non_coding_transcript_exon_variant | 18/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NSUN2 | ENST00000264670.11 | c.2271C>T | p.Gly757= | synonymous_variant | 19/19 | 1 | NM_017755.6 | P2 | |
LINC01018 | ENST00000661215.1 | n.757-162G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152252Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251364Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135858
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GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461646Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 727130
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GnomAD4 genome ? AF: 0.0000920 AC: 14AN: 152252Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74380
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 03, 2017 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 03, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at