NM_003730.6:c.710dupG
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5
The NM_003730.6(RNASET2):c.710dupG(p.Leu238SerfsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,613,054 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_003730.6 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RNASET2 | ENST00000508775.6 | c.710dupG | p.Leu238SerfsTer5 | frameshift_variant | Exon 9 of 9 | 1 | NM_003730.6 | ENSP00000426455.2 | ||
ENSG00000249141 | ENST00000507747.1 | c.432+4442dupG | intron_variant | Intron 7 of 7 | 5 | ENSP00000426906.1 |
Frequencies
GnomAD3 genomes AF: 0.0000331 AC: 5AN: 151166Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251430Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135906
GnomAD4 exome AF: 0.0000417 AC: 61AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.0000440 AC XY: 32AN XY: 727246
GnomAD4 genome AF: 0.0000331 AC: 5AN: 151166Hom.: 0 Cov.: 33 AF XY: 0.0000136 AC XY: 1AN XY: 73762
ClinVar
Submissions by phenotype
Cystic leukoencephalopathy without megalencephaly Pathogenic:1
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not specified Uncertain:1
Variant summary: RNASET2 c.710dupG (p.Leu238SerfsX5) results in a premature termination codon, predicted to cause a truncation of the encoded protein. No downstream pathogenic variants have been reported. The variant allele was found at a frequency of 2.8e-05 in 251430 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.710dupG has been reported in the literature in one individual affected with Cystic leukoencephalopathy without megalencephaly (Kuster_2017, Rice_2017). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 28924877, 27943079). ClinVar contains an entry for this variant (Variation ID: 436545). Based on the evidence outlined above, the variant was classified as uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at