rs3100586

Positions:

• chr2-232095368-T-A
• chr2-232095368-T-G

Variant summary

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

The NM_152383.5(DIS3L2):​c.601+7647T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 152,174 control chromosomes in the GnomAD database, including 48,893 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 0.80 (48893 hom., cov: 32)
• Consequence: DIS3L2 NM_152383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.870

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIS3L2	NM_152383.5	c.601+7647T>A		intron_variant		ENST00000325385.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIS3L2	ENST00000325385.12	c.601+7647T>A		intron_variant		5	NM_152383.5	P1

Frequencies

GnomAD3 genomes AF: 0.796 AC: 121047 AN: 152056 Hom.: 48834 Cov.: 32

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.796 AC: 121159 AN: 152174 Hom.: 48893 Cov.: 32 AF XY: 0.798 AC XY: 59394 AN XY: 74396

Gnomad4 AFR AF: 0.910

Gnomad4 AMR AF: 0.803

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.867

Gnomad4 NFE AF: 0.746

Gnomad4 OTH AF: 0.735

Alfa AF: 0.710 Hom.: 2103

Bravo AF: 0.800

Asia WGS AF: 0.615 AC: 2136 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.39
DANN	Benign	0.26

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: rs3100586; hg19: chr2-232960078;