rs6746834

Variant names:

• chr2-232294107-A-G
• rs6746834
• NM_152383.5:c.1660-5933A>G

Variant summary

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

The ENST00000325385.12(DIS3L2):​c.1660-5933A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,036 control chromosomes in the GnomAD database, including 8,733 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 0.31 (8733 hom., cov: 32)
• Consequence: DIS3L2 ENST00000325385.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000325385.12. 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.1660-5933A>G		intron	N/A	NP_689596.4
	DIS3L2	NM_001257281.2		c.1581+30745A>G		intron	N/A	NP_001244210.1
	DIS3L2	NR_046476.2		n.1806-5933A>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.1660-5933A>G		intron	N/A	ENSP00000315569.7
	DIS3L2	ENST00000390005.9	TSL:1	n.1660-5933A>G		intron	N/A	ENSP00000374655.5
	DIS3L2	ENST00000445090.5	TSL:1	n.*886-5933A>G		intron	N/A	ENSP00000388999.1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47775 AN: 151918 Hom.: 8702 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.315 AC: 47860 AN: 152036 Hom.: 8733 Cov.: 32 AF XY: 0.314 AC XY: 23297 AN XY: 74310

African (AFR) AF: 0.473 AC: 19629 AN: 41460

American (AMR) AF: 0.390 AC: 5962 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1030 AN: 3466

East Asian (EAS) AF: 0.498 AC: 2563 AN: 5144

South Asian (SAS) AF: 0.251 AC: 1209 AN: 4822

European-Finnish (FIN) AF: 0.173 AC: 1836 AN: 10596

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14614 AN: 67946

Other (OTH) AF: 0.318 AC: 670 AN: 2110

Alfa AF: 0.352 Hom.: 2875

Bravo AF: 0.344

Asia WGS AF: 0.349 AC: 1211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.29
PhyloP100		-0.36
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: rs6746834; hg19: chr2-233158817;