rs775532734
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_152383.5(DIS3L2):c.1638C>T(p.Asp546=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,614,028 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 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
DIS3L2
NM_152383.5 synonymous
NM_152383.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.42
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 -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 2-232263419-C-T is Benign according to our data. Variant chr2-232263419-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 241963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.42 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DIS3L2 | NM_152383.5 | c.1638C>T | p.Asp546= | synonymous_variant | 13/21 | ENST00000325385.12 | |
DIS3L2 | NM_001257281.2 | c.1581+57C>T | intron_variant | ||||
DIS3L2 | NR_046476.2 | n.1784C>T | non_coding_transcript_exon_variant | 13/21 | |||
DIS3L2 | NR_046477.2 | n.1760C>T | non_coding_transcript_exon_variant | 12/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DIS3L2 | ENST00000325385.12 | c.1638C>T | p.Asp546= | synonymous_variant | 13/21 | 5 | NM_152383.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152144Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000241 AC: 6AN: 248724Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135036
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GnomAD4 exome AF: 0.0000287 AC: 42AN: 1461884Hom.: 0 Cov.: 31 AF XY: 0.0000316 AC XY: 23AN XY: 727238
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GnomAD4 genome ? AF: 0.0000592 AC: 9AN: 152144Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74320
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
DIS3L2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 01, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Perlman syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 14, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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