chr2-232087639-C-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1
The NM_152383.5(DIS3L2):c.519C>T(p.Ser173=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,614,048 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000061 ( 0 hom. )
Consequence
DIS3L2
NM_152383.5 synonymous
NM_152383.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.90
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 -8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
Variant 2-232087639-C-T is Benign according to our data. Variant chr2-232087639-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 334931.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-1.9 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000723 (11/152168) while in subpopulation EAS AF= 0.00174 (9/5176). AF 95% confidence interval is 0.000907. There are 0 homozygotes in gnomad4. There are 7 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| DIS3L2 | NM_152383.5 | c.519C>T | p.Ser173= | synonymous_variant | 6/21 | ENST00000325385.12 | NP_689596.4 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| DIS3L2 | ENST00000325385.12 | c.519C>T | p.Ser173= | synonymous_variant | 6/21 | 5 | NM_152383.5 | ENSP00000315569 | P1 |
Frequencies
GnomAD3 genomes 0.0000723 AC: 11AN: 152050Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000441 AC: 11AN: 249498Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135348
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GnomAD4 exome AF: 0.0000609 AC: 89AN: 1461880Hom.: 0 Cov.: 32 AF XY: 0.0000509 AC XY: 37AN XY: 727240
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GnomAD4 genome 0.0000723 AC: 11AN: 152168Hom.: 0 Cov.: 31 AF XY: 0.0000941 AC XY: 7AN XY: 74408
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Perlman syndrome Uncertain:1Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
| Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not provided Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2022 | DIS3L2: BP4, BP7 - |
Computational scores
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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