2-232257702-A-G

Position:

• chr2-232257702-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152383.5(DIS3L2):​c.1426-5505A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,208 control chromosomes in the GnomAD database, including 25,723 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 (25723 hom., cov: 33)
• Consequence: DIS3L2 NM_152383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.262

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIS3L2	NM_152383.5	c.1426-5505A>G		intron_variant		ENST00000325385.12	NP_689596.4
DIS3L2	NM_001257281.2	c.1426-5505A>G		intron_variant			NP_001244210.1
DIS3L2	NR_046476.2	n.1572-5505A>G		intron_variant
DIS3L2	NR_046477.2	n.1548-5505A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIS3L2	ENST00000325385.12	c.1426-5505A>G		intron_variant		5	NM_152383.5	ENSP00000315569.7

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83478 AN: 152090 Hom.: 25661 Cov.: 33

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.549 AC: 83603 AN: 152208 Hom.: 25723 Cov.: 33 AF XY: 0.549 AC XY: 40818 AN XY: 74408

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.852

Gnomad4 SAS AF: 0.662

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.556

Alfa AF: 0.437 Hom.: 24724

Bravo AF: 0.582

Asia WGS AF: 0.791 AC: 2747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	14
DANN	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs2853362; hg19: chr2-233122412;