rs780625125

Positions:

• chr2-232334417-C-G
• chr2-232334417-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152383.5(DIS3L2):​c.2207C>G​(p.Ala736Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: DIS3L2 NM_152383.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.58

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]

DIS3L2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34918988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIS3L2	NM_152383.5	c.2207C>G	p.Ala736Gly	missense_variant	18/21	ENST00000325385.12	NP_689596.4
DIS3L2	NM_001257281.2	c.1582-8928C>G		intron_variant			NP_001244210.1
DIS3L2	NR_046476.2	n.2280C>G		non_coding_transcript_exon_variant	18/21
DIS3L2	NR_046477.2	n.2259C>G		non_coding_transcript_exon_variant	17/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIS3L2	ENST00000325385.12	c.2207C>G	p.Ala736Gly	missense_variant	18/21	5	NM_152383.5	ENSP00000315569.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;T;T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D;.;D
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Pathogenic	3.2	M;M;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.3	D;D;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.024	D;D;D
Sift4G	Uncertain	0.047	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.80
MutPred		0.45		Loss of stability (P = 0.1399);Loss of stability (P = 0.1399);.;
MVP		0.14
MPC		0.82
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.41
gMVP		0.70

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: rs780625125; hg19: chr2-233199127;