rs200027186
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP6BS1
The NM_152383.5(DIS3L2):āc.1019A>Gā(p.Tyr340Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000356 in 1,614,206 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y340H) has been classified as Uncertain significance.
Frequency
Consequence
NM_152383.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DIS3L2 | NM_152383.5 | c.1019A>G | p.Tyr340Cys | missense_variant | 9/21 | ENST00000325385.12 | |
DIS3L2 | NM_001257281.2 | c.1019A>G | p.Tyr340Cys | missense_variant | 9/14 | ||
DIS3L2 | NR_046476.2 | n.1165A>G | non_coding_transcript_exon_variant | 9/21 | |||
DIS3L2 | NR_046477.2 | n.1141A>G | non_coding_transcript_exon_variant | 8/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DIS3L2 | ENST00000325385.12 | c.1019A>G | p.Tyr340Cys | missense_variant | 9/21 | 5 | NM_152383.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000236 AC: 36AN: 152230Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000164 AC: 41AN: 249528Hom.: 0 AF XY: 0.000163 AC XY: 22AN XY: 135374
GnomAD4 exome AF: 0.000368 AC: 538AN: 1461858Hom.: 0 Cov.: 31 AF XY: 0.000375 AC XY: 273AN XY: 727224
GnomAD4 genome ? AF: 0.000236 AC: 36AN: 152348Hom.: 0 Cov.: 33 AF XY: 0.000255 AC XY: 19AN XY: 74498
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 12, 2021 | The c.1019A>G (p.Y340C) alteration is located in exon 9 (coding exon 8) of the DIS3L2 gene. This alteration results from a A to G substitution at nucleotide position 1019, causing the tyrosine (Y) at amino acid position 340 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Perlman syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at