rs17272089

Positions:

chr2-232210371-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_152383.5(DIS3L2):c.1170C>T(p.Leu390=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.025 in 1,613,548 control chromosomes in the GnomAD database, including 638 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 39 hom., cov: 32)

Exomes 𝑓: 0.026 ( 599 hom. )

Consequence

DIS3L2
NM_152383.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.681

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]

DIS3L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 2-232210371-C-T is Benign according to our data. Variant chr2-232210371-C-T is described in ClinVar as [Benign]. Clinvar id is 334936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-232210371-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.681 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0176 (2688/152304) while in subpopulation SAS AF= 0.0447 (215/4810). AF 95% confidence interval is 0.0398. There are 39 homozygotes in gnomad4. There are 1252 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DIS3L2	NM_152383.5 linkuse as main transcript	c.1170C>T	p.Leu390=	synonymous_variant	10/21	ENST00000325385.12	NP_689596.4
DIS3L2	NM_001257281.2 linkuse as main transcript	c.1170C>T	p.Leu390=	synonymous_variant	10/14		NP_001244210.1
DIS3L2	NR_046476.2 linkuse as main transcript	n.1316C>T		non_coding_transcript_exon_variant	10/21
DIS3L2	NR_046477.2 linkuse as main transcript	n.1292C>T		non_coding_transcript_exon_variant	9/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIS3L2	ENST00000325385.12 linkuse as main transcript	c.1170C>T	p.Leu390=	synonymous_variant	10/21	5	NM_152383.5	ENSP00000315569	P1	Q8IYB7-1

Frequencies

GnomAD3 genomes

AF:

0.0177

AC:

2687

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00475

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0130

Gnomad ASJ

AF:

0.0308

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0440

Gnomad FIN

AF:

0.00886

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0264

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.0215

AC:

5373

AN:

249530

Hom.:

AF XY:

0.0234

AC XY:

3166

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.00452

Gnomad AMR exome

AF:

0.0141

Gnomad ASJ exome

AF:

0.0290

Gnomad EAS exome

AF:

0.000222

Gnomad SAS exome

AF:

0.0407

Gnomad FIN exome

AF:

0.00988

Gnomad NFE exome

AF:

0.0257

Gnomad OTH exome

AF:

0.0243

GnomAD4 exome

AF:

0.0258

AC:

37725

AN:

1461244

Hom.:

599

Cov.:

AF XY:

0.0264

AC XY:

19169

AN XY:

726942

show subpopulations

Gnomad4 AFR exome

AF:

0.00442

Gnomad4 AMR exome

AF:

0.0143

Gnomad4 ASJ exome

AF:

0.0284

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0401

Gnomad4 FIN exome

AF:

0.00914

Gnomad4 NFE exome

AF:

0.0274

Gnomad4 OTH exome

AF:

0.0252

GnomAD4 genome

AF:

0.0176

AC:

2688

AN:

152304

Hom.:

Cov.:

AF XY:

0.0168

AC XY:

1252

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00474

Gnomad4 AMR

AF:

0.0131

Gnomad4 ASJ

AF:

0.0308

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0447

Gnomad4 FIN

AF:

0.00886

Gnomad4 NFE

AF:

0.0264

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.0232

Hom.:

Bravo

AF:

0.0169

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0286

EpiControl

AF:

0.0270

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

Perlman syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 22, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

5.1

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over