2-231974180-G-A

Position:

• chr2-231974180-G-A

Variant summary

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

The NM_152383.5(DIS3L2):​c.-94+12415G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,136 control chromosomes in the GnomAD database, including 1,859 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 0.13 (1859 hom., cov: 31)
• Consequence: DIS3L2 NM_152383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIS3L2	NM_152383.5	c.-94+12415G>A		intron_variant		ENST00000325385.12	NP_689596.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIS3L2	ENST00000325385.12	c.-94+12415G>A		intron_variant		5	NM_152383.5	ENSP00000315569.7

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20350 AN: 152016 Hom.: 1855 Cov.: 31

Gnomad AFR AF: 0.0346

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.0983

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.134 AC: 20355 AN: 152136 Hom.: 1859 Cov.: 31 AF XY: 0.135 AC XY: 10024 AN XY: 74376

Gnomad4 AFR AF: 0.0345

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.0983

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.175

Alfa AF: 0.177 Hom.: 5088

Bravo AF: 0.130

Asia WGS AF: 0.342 AC: 1185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.68

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: rs12988522; hg19: chr2-232838890;