NM_152383.5:c.1752G>A

Variant names:

• chr2-232329825-G-A
• rs1375650718
• NM_152383.5:c.1752G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_152383.5(DIS3L2):​c.1752G>A​(p.Glu584Glu) variant causes a synonymous 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DIS3L2 NM_152383.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.97
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 2-232329825-G-A is Benign according to our data. Variant chr2-232329825-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 531962.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.97 with no splicing effect.

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.1752G>A	p.Glu584Glu	synonymous	Exon 15 of 21	NP_689596.4
	DIS3L2	NM_001257281.2		c.1582-13520G>A		intron	N/A	NP_001244210.1
	DIS3L2	NR_046476.2		n.1886-61G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIS3L2	ENST00000325385.12	TSL:5 MANE Select	c.1752G>A	p.Glu584Glu	synonymous	Exon 15 of 21	ENSP00000315569.7
	DIS3L2	ENST00000390005.9	TSL:1	n.1740-61G>A		intron	N/A	ENSP00000374655.5
	DIS3L2	ENST00000445090.5	TSL:1	n.*966-58G>A		intron	N/A	ENSP00000388999.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 199748 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1406024 Hom.: 0 Cov.: 52 AF XY: 0.00 AC XY: 0 AN XY: 697130

African (AFR) AF: 0.00 AC: 0 AN: 31618

American (AMR) AF: 0.00 AC: 0 AN: 39012

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24274

East Asian (EAS) AF: 0.00 AC: 0 AN: 35984

South Asian (SAS) AF: 0.00 AC: 0 AN: 79246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5372

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1082072

Other (OTH) AF: 0.00 AC: 0 AN: 57972

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	12
DANN	Benign	0.71
PhyloP100		2.0
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1375650718; hg19: chr2-233194535;