NM_152383.5:c.2242C>A

Variant names:

• chr2-232334452-C-A
• rs372560799
• NM_152383.5:c.2242C>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.2242C>A​(p.Arg748Ser) 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R748C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DIS3L2 NM_152383.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00
• 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: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P

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=0.19493833).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIS3L2	NM_152383.5	MANE Select	c.2242C>A	p.Arg748Ser	missense	Exon 18 of 21	NP_689596.4
	DIS3L2	NR_046476.2		n.2315C>A		non_coding_transcript_exon	Exon 18 of 21
	DIS3L2	NR_046477.2		n.2294C>A		non_coding_transcript_exon	Exon 17 of 19

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIS3L2	ENST00000325385.12	TSL:5 MANE Select	c.2242C>A	p.Arg748Ser	missense	Exon 18 of 21	ENSP00000315569.7
	DIS3L2	ENST00000390005.9	TSL:1	n.*309C>A		non_coding_transcript_exon	Exon 18 of 21	ENSP00000374655.5
	DIS3L2	ENST00000445090.5	TSL:1	n.*1398C>A		non_coding_transcript_exon	Exon 17 of 19	ENSP00000388999.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.032
Eigen_PC	Benign	-0.059
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.0
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.081
Sift	Benign	0.050	D
Sift4G	Benign	0.32	T
Polyphen		0.18	B
Vest4		0.78
MutPred		0.45		Loss of MoRF binding (P = 0.0409)
MVP		0.043
MPC		0.48
ClinPred		0.81	D
GERP RS		2.9
PromoterAI		0.039	Neutral
Varity_R		0.27
gMVP		0.75
Mutation Taster		=66/34	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: rs372560799; hg19: chr2-233199162;