rs11887184

Positions:

• chr2-232087576-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_152383.5(DIS3L2):​c.456A>G​(p.Gln152Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0818 in 1,613,826 control chromosomes in the GnomAD database, including 6,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1098 hom., cov: 31)
  • Exomes 𝑓: 0.079 (5346 hom.)
• Consequence: DIS3L2 NM_152383.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0330

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-232087576-A-G is Benign according to our data. Variant chr2-232087576-A-G is described in ClinVar as [Benign]. Clinvar id is 262632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.033 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIS3L2	NM_152383.5	c.456A>G	p.Gln152Gln	synonymous_variant	6/21	ENST00000325385.12	NP_689596.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIS3L2	ENST00000325385.12	c.456A>G	p.Gln152Gln	synonymous_variant	6/21	5	NM_152383.5	ENSP00000315569.7

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16473 AN: 151940 Hom.: 1094 Cov.: 31

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.0370

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0700

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0708

Gnomad OTH AF: 0.101

GnomAD3 exomes AF: 0.0954 AC: 23805 AN: 249446 Hom.: 1388 AF XY: 0.0915 AC XY: 12389 AN XY: 135330

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.165

Gnomad ASJ exome AF: 0.0987

Gnomad EAS exome AF: 0.0357

Gnomad SAS exome AF: 0.110

Gnomad FIN exome AF: 0.0645

Gnomad NFE exome AF: 0.0729

Gnomad OTH exome AF: 0.0848

GnomAD4 exome AF: 0.0790 AC: 115504 AN: 1461770 Hom.: 5346 Cov.: 32 AF XY: 0.0789 AC XY: 57387 AN XY: 727180

Gnomad4 AFR exome AF: 0.194

Gnomad4 AMR exome AF: 0.163

Gnomad4 ASJ exome AF: 0.0963

Gnomad4 EAS exome AF: 0.0340

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.0685

Gnomad4 NFE exome AF: 0.0714

Gnomad4 OTH exome AF: 0.0850

GnomAD4 genome AF: 0.109 AC: 16499 AN: 152056 Hom.: 1098 Cov.: 31 AF XY: 0.107 AC XY: 7979 AN XY: 74348

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0963

Gnomad4 EAS AF: 0.0363

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.0700

Gnomad4 NFE AF: 0.0708

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0885 Hom.: 509

Bravo AF: 0.116

Asia WGS AF: 0.100 AC: 348 AN: 3478

EpiCase AF: 0.0697

EpiControl AF: 0.0668

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2019	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.99
DANN	Benign	0.39
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: rs11887184; hg19: chr2-232952286;