NM_001257281.2:c.1625dupA
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The NM_001257281.2(DIS3L2):c.1625dupA(p.His542GlnfsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000045 in 1,556,426 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000043 ( 0 hom. )
Consequence
DIS3L2
NM_001257281.2 frameshift
NM_001257281.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.395
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]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 6 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.103 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001257281.2. 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_001257281.2 | c.1625dupA | p.His542GlnfsTer6 | frameshift | Exon 14 of 14 | NP_001244210.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DIS3L2 | ENST00000273009.10 | TSL:2 | c.1625dupA | p.His542GlnfsTer6 | frameshift | Exon 14 of 14 | ENSP00000273009.6 | ||
| NRBF2P6 | ENST00000513620.1 | TSL:6 | n.273dupA | non_coding_transcript_exon | Exon 1 of 1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152202
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00000619 AC: 1AN: 161454 AF XY: 0.0000116 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
161454
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
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000427 AC: 6AN: 1404224Hom.: 0 Cov.: 30 AF XY: 0.00000577 AC XY: 4AN XY: 693152 show subpopulations
GnomAD4 exome
AF:
AC:
6
AN:
1404224
Hom.:
Cov.:
30
AF XY:
AC XY:
4
AN XY:
693152
show subpopulations
African (AFR)
AF:
AC:
0
AN:
31742
American (AMR)
AF:
AC:
0
AN:
36286
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25286
East Asian (EAS)
AF:
AC:
0
AN:
36162
South Asian (SAS)
AF:
AC:
0
AN:
79798
European-Finnish (FIN)
AF:
AC:
0
AN:
48702
Middle Eastern (MID)
AF:
AC:
0
AN:
5702
European-Non Finnish (NFE)
AF:
AC:
6
AN:
1082246
Other (OTH)
AF:
AC:
0
AN:
58300
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.517
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
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10
<30
30-35
35-40
40-45
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50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74356 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152202
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74356
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41450
American (AMR)
AF:
AC:
0
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5190
South Asian (SAS)
AF:
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
AC:
0
AN:
10618
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68032
Other (OTH)
AF:
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Perlman syndrome Uncertain:1
Feb 15, 2023
Department of Pathology and Laboratory Medicine, Sinai Health System
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:research
not provided Uncertain:1
Sep 16, 2018
Gharavi Laboratory, Columbia University
Significance:Uncertain significance
Review Status:no assertion criteria provided
Collection Method:research
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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