chr2-232169762-T-C

Variant names:

• chr2-232169762-T-C
• rs3103295
• NM_152383.5:c.1124+6130T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_152383.5(DIS3L2):​c.1124+6130T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,998 control chromosomes in the GnomAD database, including 24,455 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 0.55 (24455 hom., cov: 32)
• Consequence: DIS3L2 NM_152383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.44
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIS3L2	NM_152383.5	c.1124+6130T>C		intron_variant	Intron 9 of 20	ENST00000325385.12	NP_689596.4
DIS3L2	NM_001257281.2	c.1124+6130T>C		intron_variant	Intron 9 of 13		NP_001244210.1
DIS3L2	NR_046476.2	n.1270+6130T>C		intron_variant	Intron 9 of 20
DIS3L2	NR_046477.2	n.1246+6130T>C		intron_variant	Intron 8 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIS3L2	ENST00000325385.12	c.1124+6130T>C		intron_variant	Intron 9 of 20	5	NM_152383.5	ENSP00000315569.7

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83258 AN: 151880 Hom.: 24443 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.548 AC: 83290 AN: 151998 Hom.: 24455 Cov.: 32 AF XY: 0.554 AC XY: 41156 AN XY: 74272

African (AFR) AF: 0.333 AC: 13798 AN: 41438

American (AMR) AF: 0.623 AC: 9515 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1841 AN: 3470

East Asian (EAS) AF: 0.689 AC: 3568 AN: 5178

South Asian (SAS) AF: 0.371 AC: 1783 AN: 4810

European-Finnish (FIN) AF: 0.741 AC: 7825 AN: 10560

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.635 AC: 43172 AN: 67968

Other (OTH) AF: 0.538 AC: 1134 AN: 2106

Alfa AF: 0.599 Hom.: 37573

Bravo AF: 0.534

Asia WGS AF: 0.434 AC: 1511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.86
PhyloP100		2.4
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: rs3103295; hg19: chr2-233034472;