rs11686328

Variant names:

• chr2-232280973-G-A
• rs11686328
• NM_152383.5:c.1659+17533G>A

Variant summary

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

The NM_152383.5(DIS3L2):​c.1659+17533G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,210 control chromosomes in the GnomAD database, including 1,477 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 0.12 (1477 hom., cov: 32)
• Consequence: DIS3L2 NM_152383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIS3L2	NM_152383.5	c.1659+17533G>A		intron_variant	Intron 13 of 20	ENST00000325385.12	NP_689596.4
DIS3L2	NM_001257281.2	c.1581+17611G>A		intron_variant	Intron 13 of 13		NP_001244210.1
DIS3L2	NR_046476.2	n.1805+17533G>A		intron_variant	Intron 13 of 20
DIS3L2	NR_046477.2	n.1781+17533G>A		intron_variant	Intron 12 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIS3L2	ENST00000325385.12	c.1659+17533G>A		intron_variant	Intron 13 of 20	5	NM_152383.5	ENSP00000315569.7

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17946 AN: 152092 Hom.: 1467 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0759

Gnomad EAS AF: 0.0375

Gnomad SAS AF: 0.0547

Gnomad FIN AF: 0.0743

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0681

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.118 AC: 17997 AN: 152210 Hom.: 1477 Cov.: 32 AF XY: 0.116 AC XY: 8650 AN XY: 74444

African (AFR) AF: 0.234 AC: 9727 AN: 41500

American (AMR) AF: 0.117 AC: 1787 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0759 AC: 263 AN: 3466

East Asian (EAS) AF: 0.0368 AC: 191 AN: 5188

South Asian (SAS) AF: 0.0545 AC: 263 AN: 4826

European-Finnish (FIN) AF: 0.0743 AC: 788 AN: 10612

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0681 AC: 4634 AN: 68010

Other (OTH) AF: 0.115 AC: 243 AN: 2110

Alfa AF: 0.0821 Hom.: 1127

Bravo AF: 0.127

Asia WGS AF: 0.0800 AC: 279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.12
DANN	Benign	0.43
PhyloP100		-2.7
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: rs11686328; hg19: chr2-233145683;