NM_152383.5:c.-94+25319G>C

Variant names:

• chr2-231987084-G-C
• rs1982474
• NM_152383.5:c.-94+25319G>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.-94+25319G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,164 control chromosomes in the GnomAD database, including 2,878 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 0.13 (2878 hom., cov: 32)
• Consequence: DIS3L2 NM_152383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633
• Publications: 1 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 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.-94+25319G>C		intron	N/A	NP_689596.4
	DIS3L2	NM_001257281.2		c.-94+25319G>C		intron	N/A	NP_001244210.1
	DIS3L2	NM_001257282.2		c.-94+25319G>C		intron	N/A	NP_001244211.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIS3L2	ENST00000325385.12	TSL:5 MANE Select	c.-94+25319G>C		intron	N/A	ENSP00000315569.7
	DIS3L2	ENST00000409401.7	TSL:1	c.-94+25319G>C		intron	N/A	ENSP00000386594.3
	DIS3L2	ENST00000390005.9	TSL:1	n.-94+25319G>C		intron	N/A	ENSP00000374655.5

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19216 AN: 152046 Hom.: 2870 Cov.: 32

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.0687

Gnomad ASJ AF: 0.0461

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0547

Gnomad FIN AF: 0.0342

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0309

Gnomad OTH AF: 0.0982

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

GnomAD4 genome AF: 0.127 AC: 19253 AN: 152164 Hom.: 2878 Cov.: 32 AF XY: 0.123 AC XY: 9127 AN XY: 74392

African (AFR) AF: 0.363 AC: 15037 AN: 41474

American (AMR) AF: 0.0685 AC: 1046 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0461 AC: 160 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5178

South Asian (SAS) AF: 0.0539 AC: 260 AN: 4822

European-Finnish (FIN) AF: 0.0342 AC: 363 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0309 AC: 2104 AN: 68026

Other (OTH) AF: 0.0967 AC: 204 AN: 2110

Alfa AF: 0.0881 Hom.: 206

Bravo AF: 0.140

Asia WGS AF: 0.0560 AC: 196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.69
PhyloP100		0.63
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: rs1982474; hg19: chr2-232851794;