2-232272608-T-C

Variant names:

• chr2-232272608-T-C
• rs2633254
• NM_152383.5:c.1659+9168T>C

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+9168T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 152,166 control chromosomes in the GnomAD database, including 39,733 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 0.71 (39733 hom., cov: 33)
• Consequence: DIS3L2 NM_152383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIS3L2	NM_152383.5	c.1659+9168T>C		intron_variant	Intron 13 of 20	ENST00000325385.12	NP_689596.4
DIS3L2	NM_001257281.2	c.1581+9246T>C		intron_variant	Intron 13 of 13		NP_001244210.1
DIS3L2	NR_046476.2	n.1805+9168T>C		intron_variant	Intron 13 of 20
DIS3L2	NR_046477.2	n.1781+9168T>C		intron_variant	Intron 12 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIS3L2	ENST00000325385.12	c.1659+9168T>C		intron_variant	Intron 13 of 20	5	NM_152383.5	ENSP00000315569.7

Frequencies

GnomAD3 genomes AF: 0.710 AC: 108004 AN: 152048 Hom.: 39668 Cov.: 33

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.711 AC: 108130 AN: 152166 Hom.: 39733 Cov.: 33 AF XY: 0.709 AC XY: 52726 AN XY: 74398

African (AFR) AF: 0.894 AC: 37139 AN: 41542

American (AMR) AF: 0.716 AC: 10954 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2356 AN: 3468

East Asian (EAS) AF: 0.874 AC: 4519 AN: 5168

South Asian (SAS) AF: 0.712 AC: 3428 AN: 4816

European-Finnish (FIN) AF: 0.547 AC: 5786 AN: 10572

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.611 AC: 41573 AN: 67986

Other (OTH) AF: 0.727 AC: 1539 AN: 2116

Alfa AF: 0.639 Hom.: 37934

Bravo AF: 0.735

Asia WGS AF: 0.833 AC: 2896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.70
DANN	Benign	0.49
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: rs2633254; hg19: chr2-233137318;