rs7571816

chr2-232212354-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.1204+1949A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0796 in 152,234 control chromosomes in the GnomAD database, including 1,279 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 0.080 (1279 hom., cov: 32)
• Consequence: DIS3L2 NM_152383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIS3L2	NM_152383.5	c.1204+1949A>G		intron_variant		ENST00000325385.12
DIS3L2	NM_001257281.2	c.1204+1949A>G		intron_variant
DIS3L2	NR_046476.2	n.1350+1949A>G		intron_variant, non_coding_transcript_variant
DIS3L2	NR_046477.2	n.1326+1949A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIS3L2	ENST00000325385.12	c.1204+1949A>G		intron_variant		5	NM_152383.5	P1

Frequencies

GnomAD3 genomes AF: 0.0795 AC: 12093 AN: 152116 Hom.: 1273 Cov.: 32

Gnomad AFR AF: 0.0975

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.0814

Gnomad FIN AF: 0.0399

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0222

Gnomad OTH AF: 0.0755

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

GnomAD4 genome AF: 0.0796 AC: 12118 AN: 152234 Hom.: 1279 Cov.: 32 AF XY: 0.0868 AC XY: 6463 AN XY: 74420

Gnomad4 AFR AF: 0.0975

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.0810

Gnomad4 FIN AF: 0.0399

Gnomad4 NFE AF: 0.0222

Gnomad4 OTH AF: 0.0752

Alfa AF: 0.0445 Hom.: 1487

Bravo AF: 0.0952

Asia WGS AF: 0.225 AC: 780 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.015
Dann	Benign	0.54

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: rs7571816; hg19: chr2-233077064;