chr2-232053189-C-T

Variant names:

• chr2-232053189-C-T
• rs1453867
• NM_152383.5:c.366+23109C>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.366+23109C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 152,220 control chromosomes in the GnomAD database, including 25,537 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 0.56 (25537 hom., cov: 33)
• Consequence: DIS3L2 NM_152383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• 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: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.674 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.366+23109C>T		intron	N/A	NP_689596.4
	DIS3L2	NM_001257281.2		c.366+23109C>T		intron	N/A	NP_001244210.1	Q8IYB7-3
	DIS3L2	NM_001257282.2		c.366+23109C>T		intron	N/A	NP_001244211.1	Q8IYB7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIS3L2	ENST00000325385.12	TSL:5 MANE Select	c.366+23109C>T		intron	N/A	ENSP00000315569.7	Q8IYB7-1
	DIS3L2	ENST00000409401.7	TSL:1	c.366+23109C>T		intron	N/A	ENSP00000386594.3	Q8IYB7-4
	DIS3L2	ENST00000390005.9	TSL:1	n.366+23109C>T		intron	N/A	ENSP00000374655.5	Q8IYB7-2

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85733 AN: 152102 Hom.: 25528 Cov.: 33

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.563 AC: 85766 AN: 152220 Hom.: 25537 Cov.: 33 AF XY: 0.570 AC XY: 42426 AN XY: 74428

African (AFR) AF: 0.372 AC: 15460 AN: 41530

American (AMR) AF: 0.620 AC: 9483 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1654 AN: 3468

East Asian (EAS) AF: 0.693 AC: 3596 AN: 5190

South Asian (SAS) AF: 0.403 AC: 1941 AN: 4822

European-Finnish (FIN) AF: 0.763 AC: 8082 AN: 10594

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.644 AC: 43766 AN: 68008

Other (OTH) AF: 0.538 AC: 1138 AN: 2114

Alfa AF: 0.606 Hom.: 13391

Bravo AF: 0.546

Asia WGS AF: 0.455 AC: 1584 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	9.7
DANN	Benign	0.64
PhyloP100		-0.11
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: rs1453867; hg19: chr2-232917899;