rs763103187

chr2-232334636-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS1

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.406

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]

ACMG classification

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	UniProt
DIS3L2	NM_152383.5	c.2295T>C	p.Ser765=	synonymous_variant	19/21	ENST00000325385.12
DIS3L2	NM_001257281.2	c.1582-8709T>C		intron_variant
DIS3L2	NR_046476.2	n.2368T>C		non_coding_transcript_exon_variant	19/21
DIS3L2	NR_046477.2	n.2347T>C		non_coding_transcript_exon_variant	18/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIS3L2	ENST00000325385.12	c.2295T>C	p.Ser765=	synonymous_variant	19/21	5	NM_152383.5	P1

Frequencies

GnomAD3 genomes AF: 0.00262 AC: 393 AN: 149878 Hom.: 0 Cov.: 33

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.: 0 Cov.: 33 AF XY: 0.000642 AC XY: 455 AN XY: 709074

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.: 0 Cov.: 33 AF XY: 0.00248 AC XY: 182 AN XY: 73364

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.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	DIS3L2: BP4, BP7, BS1 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 30, 2019	- -

Perlman syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

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

Other links and lift over

dbSNP: rs763103187; hg19: chr2-233199346; COSMIC: COSV99807410; COSMIC: COSV99807410;