rs186865544
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2
The NM_152383.5(DIS3L2):āc.1447C>Gā(p.Arg483Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00114 in 1,614,146 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R483Q) has been classified as Benign.
Frequency
Consequence
NM_152383.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DIS3L2 | NM_152383.5 | c.1447C>G | p.Arg483Gly | missense_variant | 13/21 | ENST00000325385.12 | NP_689596.4 | |
DIS3L2 | NM_001257281.2 | c.1447C>G | p.Arg483Gly | missense_variant | 13/14 | NP_001244210.1 | ||
DIS3L2 | NR_046476.2 | n.1593C>G | non_coding_transcript_exon_variant | 13/21 | ||||
DIS3L2 | NR_046477.2 | n.1569C>G | non_coding_transcript_exon_variant | 12/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DIS3L2 | ENST00000325385.12 | c.1447C>G | p.Arg483Gly | missense_variant | 13/21 | 5 | NM_152383.5 | ENSP00000315569.7 |
Frequencies
GnomAD3 genomes AF: 0.000841 AC: 128AN: 152156Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000750 AC: 187AN: 249354Hom.: 0 AF XY: 0.000695 AC XY: 94AN XY: 135272
GnomAD4 exome AF: 0.00118 AC: 1720AN: 1461872Hom.: 2 Cov.: 31 AF XY: 0.00116 AC XY: 842AN XY: 727232
GnomAD4 genome AF: 0.000841 AC: 128AN: 152274Hom.: 0 Cov.: 33 AF XY: 0.000698 AC XY: 52AN XY: 74452
ClinVar
Submissions by phenotype
Perlman syndrome Uncertain:5Benign:1Other:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 12, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Victorian Clinical Genetics Services, Murdoch Childrens Research Institute | May 01, 2020 | Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as 3C-VUS. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0106 - This gene is known to be associated with autosomal recessive disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from arginine to glycine (exon 13). (N) 0251 - Variant is heterozygous. (N) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (210 Heterozygous, 0 Homozygous). (P) 0309 - Multiple alternative amino acid changes at the same position has been observed in gnomAD (highest allele count: 3631 Heterozygous, 66 Homozygous). (N) 0502 - Missense variant with conflicting in silico predictions with low conservation. (N) 0600 - Variant is located in the RNB domain (NCBI conserved domain). (N) 0710 - Comparable variants have some previous evidence for being benign (ClinVar). (B) 0804 - Variant has previously been described as variant of uncertain significance in two independent cases with consistent phenotype (ClinVar). (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant in the literature. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign - |
not provided, no classification provided | phenotyping only | GenomeConnect - Invitae Patient Insights Network | - | Variant interpreted as Uncertain significance and reported on 12-04-2017 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Mar 10, 2022 | - - |
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 15, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 23613427, 22306653, 24909261, 30256826) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2024 | DIS3L2: BP4 - |
DIS3L2-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 18, 2022 | 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at