2-232329995-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_152383.5(DIS3L2):c.1922A>G(p.Asn641Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000809 in 1,606,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_152383.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DIS3L2 | NM_152383.5 | c.1922A>G | p.Asn641Ser | missense_variant, splice_region_variant | 15/21 | ENST00000325385.12 | NP_689596.4 | |
DIS3L2 | NM_001257281.2 | c.1582-13350A>G | intron_variant | NP_001244210.1 | ||||
DIS3L2 | NR_046476.2 | n.1995A>G | splice_region_variant, non_coding_transcript_exon_variant | 15/21 | ||||
DIS3L2 | NR_046477.2 | n.1974A>G | splice_region_variant, non_coding_transcript_exon_variant | 14/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DIS3L2 | ENST00000325385.12 | c.1922A>G | p.Asn641Ser | missense_variant, splice_region_variant | 15/21 | 5 | NM_152383.5 | ENSP00000315569.7 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152212Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000123 AC: 3AN: 242968Hom.: 0 AF XY: 0.0000227 AC XY: 3AN XY: 132150
GnomAD4 exome AF: 0.00000550 AC: 8AN: 1454090Hom.: 0 Cov.: 35 AF XY: 0.00000692 AC XY: 5AN XY: 722618
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152212Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74362
ClinVar
Submissions by phenotype
Perlman syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 19, 2023 | This variant is present in population databases (rs769948942, gnomAD 0.007%). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 463082). This variant has not been reported in the literature in individuals affected with DIS3L2-related conditions. This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 641 of the DIS3L2 protein (p.Asn641Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at