rs923333

Positions:

• chr2-232218278-T-C

Variant summary

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

The NM_152383.5(DIS3L2):​c.1204+7873T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,152 control chromosomes in the GnomAD database, including 27,393 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 (27393 hom., cov: 33)
• Consequence: DIS3L2 NM_152383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIS3L2	NM_152383.5	c.1204+7873T>C		intron_variant		ENST00000325385.12
DIS3L2	NM_001257281.2	c.1204+7873T>C		intron_variant
DIS3L2	NR_046476.2	n.1350+7873T>C		intron_variant, non_coding_transcript_variant
DIS3L2	NR_046477.2	n.1326+7873T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIS3L2	ENST00000325385.12	c.1204+7873T>C		intron_variant		5	NM_152383.5	P1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85736 AN: 152034 Hom.: 27331 Cov.: 33

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.564 AC: 85857 AN: 152152 Hom.: 27393 Cov.: 33 AF XY: 0.564 AC XY: 41979 AN XY: 74394

Gnomad4 AFR AF: 0.839

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.826

Gnomad4 SAS AF: 0.711

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.570

Alfa AF: 0.503 Hom.: 2667

Bravo AF: 0.598

Asia WGS AF: 0.798 AC: 2773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.91
DANN	Benign	0.22

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: rs923333; hg19: chr2-233082988;