rs1021555252

Positions:

• chr2-232210332-C-G
• chr2-232210332-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152383.5(DIS3L2):​c.1131C>G​(p.Asp377Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DIS3L2 NM_152383.5 missense
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051856965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIS3L2	NM_152383.5	c.1131C>G	p.Asp377Glu	missense_variant	10/21	ENST00000325385.12	NP_689596.4
DIS3L2	NM_001257281.2	c.1131C>G	p.Asp377Glu	missense_variant	10/14		NP_001244210.1
DIS3L2	NR_046476.2	n.1277C>G		non_coding_transcript_exon_variant	10/21
DIS3L2	NR_046477.2	n.1253C>G		non_coding_transcript_exon_variant	9/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIS3L2	ENST00000325385.12	c.1131C>G	p.Asp377Glu	missense_variant	10/21	5	NM_152383.5	ENSP00000315569	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.64
DEOGEN2	Benign	0.028	.;T;T;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.87	D;T;.;D
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.052	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.3	N;N;N;.
MutationTaster	Benign	0.62	D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.72	N;N;N;N
REVEL	Benign	0.070
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	.;B;B;.
Vest4		0.096
MutPred		0.46		Gain of catalytic residue at D377 (P = 0.0415);Gain of catalytic residue at D377 (P = 0.0415);Gain of catalytic residue at D377 (P = 0.0415);.;
MVP		0.043
MPC		0.21
ClinPred		0.32	T
GERP RS		3.3
Varity_R		0.061
gMVP		0.36

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: rs1021555252; hg19: chr2-233075042;