5-6611781-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_017755.6(NSUN2):c.1039G>A(p.Asp347Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000223 in 1,614,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_017755.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NSUN2 | NM_017755.6 | c.1039G>A | p.Asp347Asn | missense_variant | Exon 10 of 19 | ENST00000264670.11 | NP_060225.4 | |
NSUN2 | NM_001193455.2 | c.934G>A | p.Asp312Asn | missense_variant | Exon 9 of 18 | NP_001180384.1 | ||
NSUN2 | NR_037947.2 | n.1019G>A | non_coding_transcript_exon_variant | Exon 9 of 18 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251458Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135910
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461860Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16AN XY: 727234
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74360
ClinVar
Submissions by phenotype
Intellectual disability, autosomal recessive 5 Uncertain:1
This 6 year old female with developmental delays, microcephaly, craniosynostosis, hypertrophic cardiomyopathy, and history of acute lymphoid leukemia in remission is a compound heterozygote for 2 VUSs in the NSUN2 gene (p.Asp347Asn and p.Gly371Glu). The p.Asp347Asn variant is present in gnomAD non-Finnish European population at a frequency of 0.0024%. Computational prediction models are inconsistent. Clinical correlation was thought to be poor given the patient's history of craniosynostosis and hypertrophic cardiomyopathy, which have not been reported with biallelic pathogenic variants in NSUN2. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at