2-232343350-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1

The NM_001257281.2(DIS3L2):​c.1587C>T​(p.Asn529Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00023 in 1,555,946 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

DIS3L2
NM_001257281.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.395
Variant links:
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]
NRBF2P6 (HGNC:54797): (NRBF2 pseudogene 6)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
Variant 2-232343350-C-T is Benign according to our data. Variant chr2-232343350-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1692602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.395 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00114 (173/152296) while in subpopulation AFR AF= 0.00375 (156/41564). AF 95% confidence interval is 0.00327. There are 1 homozygotes in gnomad4. There are 79 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DIS3L2NM_001257281.2 linkc.1587C>T p.Asn529Asn synonymous_variant Exon 14 of 14 NP_001244210.1 Q8IYB7-3
NRBF2P6 n.232343350C>T intragenic_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DIS3L2ENST00000273009.10 linkc.1587C>T p.Asn529Asn synonymous_variant Exon 14 of 14 2 ENSP00000273009.6 Q8IYB7-3
NRBF2P6ENST00000513620.1 linkn.235C>T non_coding_transcript_exon_variant Exon 1 of 1 6

Frequencies

GnomAD3 genomes
AF:
0.00114
AC:
173
AN:
152178
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00376
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000293
AC:
49
AN:
167434
Hom.:
0
AF XY:
0.000289
AC XY:
26
AN XY:
90004
show subpopulations
Gnomad AFR exome
AF:
0.00363
Gnomad AMR exome
AF:
0.000349
Gnomad ASJ exome
AF:
0.000116
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000568
Gnomad NFE exome
AF:
0.000119
Gnomad OTH exome
AF:
0.000214
GnomAD4 exome
AF:
0.000132
AC:
185
AN:
1403650
Hom.:
0
Cov.:
30
AF XY:
0.000118
AC XY:
82
AN XY:
692074
show subpopulations
Gnomad4 AFR exome
AF:
0.00347
Gnomad4 AMR exome
AF:
0.000326
Gnomad4 ASJ exome
AF:
0.0000395
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000204
Gnomad4 NFE exome
AF:
0.0000417
Gnomad4 OTH exome
AF:
0.000275
GnomAD4 genome
AF:
0.00114
AC:
173
AN:
152296
Hom.:
1
Cov.:
33
AF XY:
0.00106
AC XY:
79
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.00375
Gnomad4 AMR
AF:
0.000588
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00116
Hom.:
0
Bravo
AF:
0.00113
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Perlman syndrome Benign:1
Jan 25, 2022
Sema4, Sema4
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: curation

- -

not provided Benign:1
Sep 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

DIS3L2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.64
CADD
Benign
4.3
DANN
Benign
0.46

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs556095213; hg19: chr2-233208060; API