2-232290400-T-C

Variant names:

• chr2-232290400-T-C
• rs6717918
• NM_152383.5:c.1660-9640T>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.1660-9640T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,114 control chromosomes in the GnomAD database, including 16,755 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 0.41 (16755 hom., cov: 32)
• Consequence: DIS3L2 NM_152383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 22 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: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 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.1660-9640T>C		intron	N/A	NP_689596.4
	DIS3L2	NM_001257281.2		c.1581+27038T>C		intron	N/A	NP_001244210.1	Q8IYB7-3
	DIS3L2	NR_046476.2		n.1806-9640T>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.1660-9640T>C		intron	N/A	ENSP00000315569.7	Q8IYB7-1
	DIS3L2	ENST00000390005.9	TSL:1	n.1660-9640T>C		intron	N/A	ENSP00000374655.5	Q8IYB7-2
	DIS3L2	ENST00000445090.5	TSL:1	n.*886-9640T>C		intron	N/A	ENSP00000388999.1	Q8IYB7-4

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62905 AN: 151996 Hom.: 16708 Cov.: 32

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.379

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

GnomAD4 genome AF: 0.414 AC: 63020 AN: 152114 Hom.: 16755 Cov.: 32 AF XY: 0.411 AC XY: 30573 AN XY: 74386

African (AFR) AF: 0.751 AC: 31158 AN: 41498

American (AMR) AF: 0.432 AC: 6595 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1061 AN: 3464

East Asian (EAS) AF: 0.499 AC: 2577 AN: 5168

South Asian (SAS) AF: 0.307 AC: 1480 AN: 4826

European-Finnish (FIN) AF: 0.208 AC: 2201 AN: 10600

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16740 AN: 67972

Other (OTH) AF: 0.381 AC: 802 AN: 2106

Alfa AF: 0.294 Hom.: 26379

Bravo AF: 0.451

Asia WGS AF: 0.401 AC: 1395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.56
DANN	Benign	0.33
PhyloP100		-0.29
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: rs6717918; hg19: chr2-233155110;