rs3103296

Variant names:

• chr2-232169785-T-C
• rs3103296
• NM_152383.5:c.1124+6153T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_152383.5(DIS3L2):​c.1124+6153T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 152,054 control chromosomes in the GnomAD database, including 24,479 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 0.55 (24479 hom., cov: 32)
• Consequence: DIS3L2 NM_152383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.81
• Publications: 7 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152383.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIS3L2	NM_152383.5	MANE Select	c.1124+6153T>C		intron	N/A	NP_689596.4
	DIS3L2	NM_001257281.2		c.1124+6153T>C		intron	N/A	NP_001244210.1
	DIS3L2	NR_046476.2		n.1270+6153T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIS3L2	ENST00000325385.12	TSL:5 MANE Select	c.1124+6153T>C		intron	N/A	ENSP00000315569.7
	DIS3L2	ENST00000390005.9	TSL:1	n.1124+6153T>C		intron	N/A	ENSP00000374655.5
	DIS3L2	ENST00000445090.5	TSL:1	n.*350+6153T>C		intron	N/A	ENSP00000388999.1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83313 AN: 151936 Hom.: 24467 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.548 AC: 83345 AN: 152054 Hom.: 24479 Cov.: 32 AF XY: 0.554 AC XY: 41188 AN XY: 74306

African (AFR) AF: 0.333 AC: 13797 AN: 41444

American (AMR) AF: 0.624 AC: 9534 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1841 AN: 3472

East Asian (EAS) AF: 0.689 AC: 3565 AN: 5172

South Asian (SAS) AF: 0.372 AC: 1788 AN: 4810

European-Finnish (FIN) AF: 0.741 AC: 7831 AN: 10568

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.635 AC: 43199 AN: 67996

Other (OTH) AF: 0.539 AC: 1138 AN: 2112

Alfa AF: 0.598 Hom.: 16972

Bravo AF: 0.534

Asia WGS AF: 0.434 AC: 1511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Benign	0.83
PhyloP100		2.8
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: rs3103296; hg19: chr2-233034495;