rs1438379709
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_152383.5(DIS3L2):āc.1712A>Cā(p.His571Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,198 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 Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H571L) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DIS3L2 | NM_152383.5 | c.1712A>C | p.His571Pro | missense_variant | 14/21 | ENST00000325385.12 | |
DIS3L2 | NM_001257281.2 | c.1581+36730A>C | intron_variant | ||||
DIS3L2 | NR_046476.2 | n.1858A>C | non_coding_transcript_exon_variant | 14/21 | |||
DIS3L2 | NR_046477.2 | n.1834A>C | non_coding_transcript_exon_variant | 13/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DIS3L2 | ENST00000325385.12 | c.1712A>C | p.His571Pro | missense_variant | 14/21 | 5 | NM_152383.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74350
ClinVar
Submissions by phenotype
Perlman syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 20, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1013878). This variant has not been reported in the literature in individuals affected with DIS3L2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 571 of the DIS3L2 protein (p.His571Pro). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at