Variant 2-232334636-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1

The NM_152383.5(DIS3L2):c.2295T>C(p.Ser765=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 149,990 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: 𝑓 0.0026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00066 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DIS3L2
NM_152383.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.406

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 2-232334636-T-C is Benign according to our data. Variant chr2-232334636-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 241973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.406 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00262 (393/149990) while in subpopulation AFR AF= 0.00913 (363/39754). AF 95% confidence interval is 0.00836. There are 0 homozygotes in gnomad4. There are 182 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DIS3L2	NM_152383.5 linkuse as main transcript	c.2295T>C	p.Ser765=	synonymous_variant	19/21	ENST00000325385.12	NP_689596.4
DIS3L2	NM_001257281.2 linkuse as main transcript	c.1582-8709T>C		intron_variant			NP_001244210.1
DIS3L2	NR_046476.2 linkuse as main transcript	n.2368T>C		non_coding_transcript_exon_variant	19/21
DIS3L2	NR_046477.2 linkuse as main transcript	n.2347T>C		non_coding_transcript_exon_variant	18/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIS3L2	ENST00000325385.12 linkuse as main transcript	c.2295T>C	p.Ser765=	synonymous_variant	19/21	5	NM_152383.5	ENSP00000315569	P1	Q8IYB7-1

Frequencies

GnomAD3 genomes

AF:

0.00262

AC:

393

AN:

149878

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00916

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.000786

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000737

Gnomad OTH

AF:

0.00146

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000656

AC:

937

AN:

1427840

Hom.:

Cov.:

AF XY:

0.000642

AC XY:

455

AN XY:

709074

show subpopulations

Gnomad4 AFR exome

AF:

0.0155

Gnomad4 AMR exome

AF:

0.00172

Gnomad4 ASJ exome

AF:

0.000118

Gnomad4 EAS exome

AF:

0.00140

Gnomad4 SAS exome

AF:

0.000533

Gnomad4 FIN exome

AF:

0.000292

Gnomad4 NFE exome

AF:

0.000163

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.00262

AC:

393

AN:

149990

Hom.:

Cov.:

AF XY:

0.00248

AC XY:

182

AN XY:

73364

show subpopulations

Gnomad4 AFR

AF:

0.00913

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.000788

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000737

Gnomad4 OTH

AF:

0.00145

Alfa

AF:

0.00233

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	DIS3L2: BP4, BP7, BS1 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 30, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Perlman syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

2.4

DANN

Benign

0.60

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