NM_152383.5:c.1656T>A

Variant names:

• chr2-232263437-T-A
• rs1553541570
• NM_152383.5:c.1656T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152383.5(DIS3L2):​c.1656T>A​(p.Asp552Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DIS3L2 NM_152383.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.400
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Perlman syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24841508).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152383.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIS3L2	NM_152383.5	MANE Select	c.1656T>A	p.Asp552Glu	missense	Exon 13 of 21	NP_689596.4
	DIS3L2	NM_001257281.2		c.1581+75T>A		intron	N/A	NP_001244210.1	Q8IYB7-3
	DIS3L2	NR_046476.2		n.1802T>A		non_coding_transcript_exon	Exon 13 of 21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIS3L2	ENST00000325385.12	TSL:5 MANE Select	c.1656T>A	p.Asp552Glu	missense	Exon 13 of 21	ENSP00000315569.7	Q8IYB7-1
	DIS3L2	ENST00000390005.9	TSL:1	n.1656T>A		non_coding_transcript_exon	Exon 13 of 21	ENSP00000374655.5	Q8IYB7-2
	DIS3L2	ENST00000445090.5	TSL:1	n.*882T>A		non_coding_transcript_exon	Exon 12 of 19	ENSP00000388999.1	Q8IYB7-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Perlman syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.41
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.91	L
PhyloP100		0.40
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.18
Sift	Benign	0.25	T
Sift4G	Benign	0.21	T
Polyphen		0.047	B
Vest4		0.52
MutPred		0.60		Gain of sheet (P = 0.0827)
MVP		0.29
MPC		0.63
ClinPred		0.85	D
GERP RS		1.6
Varity_R		0.48
gMVP		0.41
Mutation Taster		=56/44	polymorphism

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

Other links and lift over

dbSNP: rs1553541570; hg19: chr2-233128147;