rs17272089
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_152383.5(DIS3L2):c.1170C>T(p.Leu390=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.025 in 1,613,548 control chromosomes in the GnomAD database, including 638 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.018 ( 39 hom., cov: 32)
Exomes 𝑓: 0.026 ( 599 hom. )
Consequence
DIS3L2
NM_152383.5 synonymous
NM_152383.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.681
Genes affected
DIS3L2 (HGNC:28648): (DIS3 like 3'-5' exoribonuclease 2) The protein encoded by this gene is similar in sequence to 3'/5' exonucleolytic subunits of the RNA exosome. The exosome is a large multimeric ribonucleotide complex responsible for degrading various RNA substrates. Several transcript variants, some protein-coding and some not, have been found for this gene. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
?
Variant 2-232210371-C-T is Benign according to our data. Variant chr2-232210371-C-T is described in ClinVar as [Benign]. Clinvar id is 334936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-232210371-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.681 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0176 (2688/152304) while in subpopulation SAS AF= 0.0447 (215/4810). AF 95% confidence interval is 0.0398. There are 39 homozygotes in gnomad4. There are 1252 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 39 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DIS3L2 | NM_152383.5 | c.1170C>T | p.Leu390= | synonymous_variant | 10/21 | ENST00000325385.12 | |
DIS3L2 | NM_001257281.2 | c.1170C>T | p.Leu390= | synonymous_variant | 10/14 | ||
DIS3L2 | NR_046476.2 | n.1316C>T | non_coding_transcript_exon_variant | 10/21 | |||
DIS3L2 | NR_046477.2 | n.1292C>T | non_coding_transcript_exon_variant | 9/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DIS3L2 | ENST00000325385.12 | c.1170C>T | p.Leu390= | synonymous_variant | 10/21 | 5 | NM_152383.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0177 AC: 2687AN: 152186Hom.: 39 Cov.: 32
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GnomAD3 exomes AF: 0.0215 AC: 5373AN: 249530Hom.: 91 AF XY: 0.0234 AC XY: 3166AN XY: 135382
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GnomAD4 exome AF: 0.0258 AC: 37725AN: 1461244Hom.: 599 Cov.: 31 AF XY: 0.0264 AC XY: 19169AN XY: 726942
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GnomAD4 genome ? AF: 0.0176 AC: 2688AN: 152304Hom.: 39 Cov.: 32 AF XY: 0.0168 AC XY: 1252AN XY: 74464
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Perlman syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 22, 2021 | - - |
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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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at