rs13020779

Variant names:

• chr2-232284890-A-G
• rs13020779
• NM_152383.5:c.1660-15150A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152383.5(DIS3L2):​c.1660-15150A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,996 control chromosomes in the GnomAD database, including 9,640 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (9640 hom., cov: 32)
• Consequence: DIS3L2 NM_152383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• Perlman syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIS3L2	NM_152383.5	c.1660-15150A>G		intron_variant	Intron 13 of 20	ENST00000325385.12	NP_689596.4
DIS3L2	NM_001257281.2	c.1581+21528A>G		intron_variant	Intron 13 of 13		NP_001244210.1
DIS3L2	NR_046476.2	n.1806-15150A>G		intron_variant	Intron 13 of 20
DIS3L2	NR_046477.2	n.1782-15150A>G		intron_variant	Intron 12 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIS3L2	ENST00000325385.12	c.1660-15150A>G		intron_variant	Intron 13 of 20	5	NM_152383.5	ENSP00000315569.7

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49565 AN: 151878 Hom.: 9611 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.326

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.327 AC: 49650 AN: 151996 Hom.: 9640 Cov.: 32 AF XY: 0.326 AC XY: 24203 AN XY: 74298

African (AFR) AF: 0.519 AC: 21498 AN: 41432

American (AMR) AF: 0.393 AC: 5996 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1006 AN: 3468

East Asian (EAS) AF: 0.488 AC: 2509 AN: 5142

South Asian (SAS) AF: 0.250 AC: 1204 AN: 4814

European-Finnish (FIN) AF: 0.174 AC: 1835 AN: 10576

Middle Eastern (MID) AF: 0.281 AC: 82 AN: 292

European-Non Finnish (NFE) AF: 0.214 AC: 14559 AN: 67982

Other (OTH) AF: 0.329 AC: 695 AN: 2110

Alfa AF: 0.261 Hom.: 10539

Bravo AF: 0.356

Asia WGS AF: 0.344 AC: 1197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.6
DANN	Benign	0.43
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13020779; hg19: chr2-233149600;