2-232336580-AAGGAGG-AAGG
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The ENST00000325385.12(DIS3L2):c.2620_2622delGAG(p.Glu874del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000213 in 1,456,852 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
DIS3L2
ENST00000325385.12 conservative_inframe_deletion
ENST00000325385.12 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.660
Publications
0 publications found
Genes affected
DIS3L2 (HGNC:28648): (DIS3 like 3'-5' exoribonuclease 2) The protein encoded by this gene is similar in sequence to 3'/5' exonucleolytic subunits of the RNA exosome. The exosome is a large multimeric ribonucleotide complex responsible for degrading various RNA substrates. Several transcript variants, some protein-coding and some not, have been found for this gene. [provided by RefSeq, Mar 2012]
DIS3L2 Gene-Disease associations (from GenCC):
- Perlman syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in ENST00000325385.12. Strenght limited to Supporting due to length of the change: 1aa.
Variant Effect in Transcripts
ACMG analysis was done for transcript: ENST00000325385.12. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DIS3L2 | NM_152383.5 | MANE Select | c.2620_2622delGAG | p.Glu874del | conservative_inframe_deletion | Exon 21 of 21 | NP_689596.4 | ||
| DIS3L2 | NR_046476.2 | n.2693_2695delGAG | non_coding_transcript_exon | Exon 21 of 21 | |||||
| DIS3L2 | NR_046477.2 | n.3266_3268delGAG | non_coding_transcript_exon | Exon 19 of 19 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DIS3L2 | ENST00000325385.12 | TSL:5 MANE Select | c.2620_2622delGAG | p.Glu874del | conservative_inframe_deletion | Exon 21 of 21 | ENSP00000315569.7 | ||
| DIS3L2 | ENST00000390005.9 | TSL:1 | n.*687_*689delGAG | non_coding_transcript_exon | Exon 21 of 21 | ENSP00000374655.5 | |||
| DIS3L2 | ENST00000390005.9 | TSL:1 | n.*687_*689delGAG | 3_prime_UTR | Exon 21 of 21 | ENSP00000374655.5 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00000411 AC: 1AN: 243444 AF XY: 0.00000751 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
243444
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000213 AC: 31AN: 1456852Hom.: 0 AF XY: 0.0000248 AC XY: 18AN XY: 724950 show subpopulations
GnomAD4 exome
AF:
AC:
31
AN:
1456852
Hom.:
AF XY:
AC XY:
18
AN XY:
724950
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33464
American (AMR)
AF:
AC:
0
AN:
44714
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26130
East Asian (EAS)
AF:
AC:
0
AN:
39696
South Asian (SAS)
AF:
AC:
6
AN:
86246
European-Finnish (FIN)
AF:
AC:
0
AN:
48620
Middle Eastern (MID)
AF:
AC:
0
AN:
5726
European-Non Finnish (NFE)
AF:
AC:
25
AN:
1111918
Other (OTH)
AF:
AC:
0
AN:
60338
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.483
Heterozygous variant carriers
0
3
5
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0.00
0.20
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
Significance:Uncertain significance
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
-
2
-
Perlman syndrome (2)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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