rs377644356
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_152383.5(DIS3L2):c.1680G>A(p.Leu560=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000102 in 1,613,580 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). Synonymous variant affecting the same amino acid position (i.e. L560L) has been classified as Likely benign.
Frequency
Consequence
NM_152383.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DIS3L2 | NM_152383.5 | c.1680G>A | p.Leu560= | synonymous_variant | 14/21 | ENST00000325385.12 | |
DIS3L2 | NM_001257281.2 | c.1581+36698G>A | intron_variant | ||||
DIS3L2 | NR_046476.2 | n.1826G>A | non_coding_transcript_exon_variant | 14/21 | |||
DIS3L2 | NR_046477.2 | n.1802G>A | non_coding_transcript_exon_variant | 13/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DIS3L2 | ENST00000325385.12 | c.1680G>A | p.Leu560= | synonymous_variant | 14/21 | 5 | NM_152383.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152090Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000157 AC: 39AN: 248966Hom.: 1 AF XY: 0.000126 AC XY: 17AN XY: 135068
GnomAD4 exome AF: 0.000104 AC: 152AN: 1461490Hom.: 2 Cov.: 30 AF XY: 0.000113 AC XY: 82AN XY: 727026
GnomAD4 genome AF: 0.0000789 AC: 12AN: 152090Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74290
ClinVar
Submissions by phenotype
Perlman syndrome Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Jun 03, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 07, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
DIS3L2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 11, 2019 | 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