rs3116179

Variant names:

• chr2-232156434-A-G
• rs3116179
• NM_152383.5:c.951-7025A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-232156434-A-G
• chr2-232156434-A-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.951-7025A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 151,798 control chromosomes in the GnomAD database, including 46,993 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 0.78 (46993 hom., cov: 30)
• Consequence: DIS3L2 NM_152383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• Publications: 3 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 = 0.879 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIS3L2	NM_152383.5	MANE Select	c.951-7025A>G		intron	N/A	NP_689596.4
	DIS3L2	NM_001257281.2		c.951-7025A>G		intron	N/A	NP_001244210.1
	DIS3L2	NR_046476.2		n.1097-7025A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIS3L2	ENST00000325385.12	TSL:5 MANE Select	c.951-7025A>G		intron	N/A	ENSP00000315569.7
	DIS3L2	ENST00000390005.9	TSL:1	n.951-7025A>G		intron	N/A	ENSP00000374655.5
	DIS3L2	ENST00000445090.5	TSL:1	n.*177-7025A>G		intron	N/A	ENSP00000388999.1

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118638 AN: 151684 Hom.: 46931 Cov.: 30

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.730

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

GnomAD4 genome AF: 0.782 AC: 118754 AN: 151798 Hom.: 46993 Cov.: 30 AF XY: 0.785 AC XY: 58259 AN XY: 74220

African (AFR) AF: 0.887 AC: 36754 AN: 41436

American (AMR) AF: 0.800 AC: 12199 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2244 AN: 3466

East Asian (EAS) AF: 0.724 AC: 3739 AN: 5166

South Asian (SAS) AF: 0.562 AC: 2707 AN: 4818

European-Finnish (FIN) AF: 0.846 AC: 8843 AN: 10458

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.734 AC: 49822 AN: 67882

Other (OTH) AF: 0.728 AC: 1539 AN: 2114

Alfa AF: 0.751 Hom.: 5985

Bravo AF: 0.788

Asia WGS AF: 0.603 AC: 2092 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.50
DANN	Benign	0.63
PhyloP100		-0.38
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: rs3116179; hg19: chr2-233021144;