rs770702636
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_152383.5(DIS3L2):c.1693G>A(p.Gly565Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000161 in 1,613,756 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G565E) has been classified as Uncertain significance.
Frequency
Consequence
NM_152383.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DIS3L2 | NM_152383.5 | c.1693G>A | p.Gly565Arg | missense_variant | 14/21 | ENST00000325385.12 | |
DIS3L2 | NM_001257281.2 | c.1581+36711G>A | intron_variant | ||||
DIS3L2 | NR_046476.2 | n.1839G>A | non_coding_transcript_exon_variant | 14/21 | |||
DIS3L2 | NR_046477.2 | n.1815G>A | non_coding_transcript_exon_variant | 13/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DIS3L2 | ENST00000325385.12 | c.1693G>A | p.Gly565Arg | missense_variant | 14/21 | 5 | NM_152383.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152158Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000321 AC: 8AN: 248986Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 135070
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461598Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 727076
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74326
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 01, 2023 | The c.1693G>A (p.G565R) alteration is located in exon 14 (coding exon 13) of the DIS3L2 gene. This alteration results from a G to A substitution at nucleotide position 1693, causing the glycine (G) at amino acid position 565 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Perlman syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 565 of the DIS3L2 protein (p.Gly565Arg). This variant is present in population databases (rs770702636, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with DIS3L2-related conditions. ClinVar contains an entry for this variant (Variation ID: 410748). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DIS3L2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at