chr2-231987084-G-C

Position:

• chr2-231987084-G-C

Variant summary

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

The NM_152383.5(DIS3L2):​c.-94+25319G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,164 control chromosomes in the GnomAD database, including 2,878 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 (2878 hom., cov: 32)
• Consequence: DIS3L2 NM_152383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIS3L2	NM_152383.5	c.-94+25319G>C		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+25319G>C		intron_variant		5	NM_152383.5	ENSP00000315569	P1
	ENST00000413841.1	n.101-8306C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19216 AN: 152046 Hom.: 2870 Cov.: 32

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.0687

Gnomad ASJ AF: 0.0461

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0547

Gnomad FIN AF: 0.0342

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0309

Gnomad OTH AF: 0.0982

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

GnomAD4 genome AF: 0.127 AC: 19253 AN: 152164 Hom.: 2878 Cov.: 32 AF XY: 0.123 AC XY: 9127 AN XY: 74392

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.0685

Gnomad4 ASJ AF: 0.0461

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0539

Gnomad4 FIN AF: 0.0342

Gnomad4 NFE AF: 0.0309

Gnomad4 OTH AF: 0.0967

Alfa AF: 0.0881 Hom.: 206

Bravo AF: 0.140

Asia WGS AF: 0.0560 AC: 196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.69

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: rs1982474; hg19: chr2-232851794;