rs764957786

Variant names:

• chr2-232015563-C-A
• rs764957786
• NM_152383.5:c.102C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-232015563-C-A
• chr2-232015563-C-T

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.102C>A​(p.Asp34Glu) 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. D34A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DIS3L2 NM_152383.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.772
• 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

ENSG00000227033 (HGNC:):

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=0.10137349).

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.102C>A	p.Asp34Glu	missense	Exon 3 of 21	NP_689596.4
	DIS3L2	NM_001257281.2		c.102C>A	p.Asp34Glu	missense	Exon 3 of 14	NP_001244210.1
	DIS3L2	NM_001257282.2		c.102C>A	p.Asp34Glu	missense	Exon 3 of 7	NP_001244211.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIS3L2	ENST00000325385.12	TSL:5 MANE Select	c.102C>A	p.Asp34Glu	missense	Exon 3 of 21	ENSP00000315569.7
	DIS3L2	ENST00000409401.7	TSL:1	c.102C>A	p.Asp34Glu	missense	Exon 3 of 7	ENSP00000386594.3
	DIS3L2	ENST00000390005.9	TSL:1	n.102C>A		non_coding_transcript_exon	Exon 3 of 21	ENSP00000374655.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.012
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.77
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.025
Sift	Benign	0.040	D
Sift4G	Benign	0.31	T
Polyphen		0.13	B
Vest4		0.35
MutPred		0.18		Gain of loop (P = 0.0435)
MVP		0.10
MPC		0.25
ClinPred		0.80	D
GERP RS		4.8
Varity_R		0.064
gMVP		0.21
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs764957786; hg19: chr2-232880273;