NM_152383.5:c.1308G>T

Variant names:

• chr2-232238636-G-T
• NM_152383.5:c.1308G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152383.5(DIS3L2):​c.1308G>T​(p.Leu436Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DIS3L2 NM_152383.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.894

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIS3L2	NM_152383.5	c.1308G>T	p.Leu436Phe	missense_variant	Exon 11 of 21	ENST00000325385.12	NP_689596.4
DIS3L2	NM_001257281.2	c.1308G>T	p.Leu436Phe	missense_variant	Exon 11 of 14		NP_001244210.1
DIS3L2	NR_046476.2	n.1454G>T		non_coding_transcript_exon_variant	Exon 11 of 21
DIS3L2	NR_046477.2	n.1430G>T		non_coding_transcript_exon_variant	Exon 10 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIS3L2	ENST00000325385.12	c.1308G>T	p.Leu436Phe	missense_variant	Exon 11 of 21	5	NM_152383.5	ENSP00000315569.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460388 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726544

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	.;T;T;T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Pathogenic	1.0	D;D;.;D
M_CAP	Benign	0.031	D
MetaRNN	Pathogenic	0.89	D;D;D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.8	L;L;L;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.5	D;D;D;D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0040	D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		1.0	.;D;D;.
Vest4		0.76
MutPred		0.86		Gain of catalytic residue at Q438 (P = 0.1701);Gain of catalytic residue at Q438 (P = 0.1701);Gain of catalytic residue at Q438 (P = 0.1701);.;
MVP		0.41
MPC		0.86
ClinPred		0.97	D
GERP RS		5.7
Varity_R		0.37
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-233103346;