chr2-232163564-A-G
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_152383.5(DIS3L2):c.1056A>G(p.Leu352Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,822 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 Likely benign (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
DIS3L2
NM_152383.5 synonymous
NM_152383.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.67
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
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
Variant 2-232163564-A-G is Benign according to our data. Variant chr2-232163564-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 531977.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=2.67 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_152383.5. 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.1056A>G | p.Leu352Leu | synonymous | Exon 9 of 21 | NP_689596.4 | ||
| DIS3L2 | NM_001257281.2 | c.1056A>G | p.Leu352Leu | synonymous | Exon 9 of 14 | NP_001244210.1 | |||
| DIS3L2 | NR_046476.2 | n.1202A>G | non_coding_transcript_exon | Exon 9 of 21 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DIS3L2 | ENST00000325385.12 | TSL:5 MANE Select | c.1056A>G | p.Leu352Leu | synonymous | Exon 9 of 21 | ENSP00000315569.7 | ||
| DIS3L2 | ENST00000390005.9 | TSL:1 | n.1056A>G | non_coding_transcript_exon | Exon 9 of 21 | ENSP00000374655.5 | |||
| DIS3L2 | ENST00000445090.5 | TSL:1 | n.*282A>G | non_coding_transcript_exon | Exon 8 of 19 | ENSP00000388999.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00000802 AC: 2AN: 249500 AF XY: 0.00000739 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
249500
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: 0.00000137 AC: 2AN: 1461822Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727208 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1461822
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
727208
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33478
American (AMR)
AF:
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26134
East Asian (EAS)
AF:
AC:
0
AN:
39696
South Asian (SAS)
AF:
AC:
0
AN:
86250
European-Finnish (FIN)
AF:
AC:
0
AN:
53414
Middle Eastern (MID)
AF:
AC:
0
AN:
5742
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1111994
Other (OTH)
AF:
AC:
0
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.550
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions as Germline
Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
Perlman syndrome (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
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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