rs778990530
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_152383.5(DIS3L2):c.1994G>A(p.Cys665Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00011 in 1,611,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 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. C665F) has been classified as Uncertain significance.
Frequency
Consequence
NM_152383.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DIS3L2 | NM_152383.5 | c.1994G>A | p.Cys665Tyr | missense_variant | 16/21 | ENST00000325385.12 | |
DIS3L2 | NM_001257281.2 | c.1582-12585G>A | intron_variant | ||||
DIS3L2 | NR_046476.2 | n.2067G>A | non_coding_transcript_exon_variant | 16/21 | |||
DIS3L2 | NR_046477.2 | n.2046G>A | non_coding_transcript_exon_variant | 15/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DIS3L2 | ENST00000325385.12 | c.1994G>A | p.Cys665Tyr | missense_variant | 16/21 | 5 | NM_152383.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000985 AC: 15AN: 152248Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000101 AC: 25AN: 247138Hom.: 0 AF XY: 0.0000819 AC XY: 11AN XY: 134358
GnomAD4 exome AF: 0.000111 AC: 162AN: 1459724Hom.: 0 Cov.: 31 AF XY: 0.000113 AC XY: 82AN XY: 726294
GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74372
ClinVar
Submissions by phenotype
Perlman syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 30, 2020 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2023 | This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 665 of the DIS3L2 protein (p.Cys665Tyr). This variant is present in population databases (rs778990530, gnomAD 0.02%). 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: 410763). 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 with a negative predictive value of 80%. 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