rs3100608

Variant names:

• chr2-231985093-C-T
• rs3100608
• NM_152383.5:c.-94+23328C>T

Variant summary

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

The NM_152383.5(DIS3L2):​c.-94+23328C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 152,228 control chromosomes in the GnomAD database, including 49,316 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 0.80 (49316 hom., cov: 32)
• Consequence: DIS3L2 NM_152383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.366
• Publications: 10 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

ENSG00000227033 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIS3L2	NM_152383.5	c.-94+23328C>T		intron_variant	Intron 1 of 20	ENST00000325385.12	NP_689596.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIS3L2	ENST00000325385.12	c.-94+23328C>T		intron_variant	Intron 1 of 20	5	NM_152383.5	ENSP00000315569.7

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121526 AN: 152110 Hom.: 49255 Cov.: 32

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.731

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.868

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.799 AC: 121640 AN: 152228 Hom.: 49316 Cov.: 32 AF XY: 0.801 AC XY: 59612 AN XY: 74414

African (AFR) AF: 0.922 AC: 38290 AN: 41540

American (AMR) AF: 0.805 AC: 12308 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2158 AN: 3468

East Asian (EAS) AF: 0.731 AC: 3775 AN: 5162

South Asian (SAS) AF: 0.563 AC: 2712 AN: 4818

European-Finnish (FIN) AF: 0.868 AC: 9202 AN: 10604

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.746 AC: 50729 AN: 68020

Other (OTH) AF: 0.741 AC: 1566 AN: 2114

Alfa AF: 0.752 Hom.: 27477

Bravo AF: 0.803

Asia WGS AF: 0.619 AC: 2156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.41
PhyloP100		-0.37
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: rs3100608; hg19: chr2-232849803;