rs11887184

Variant names:

• chr2-232087576-A-G
• rs11887184
• NM_152383.5:c.456A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_152383.5(DIS3L2):​c.456A>G​(p.Gln152Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0818 in 1,613,826 control chromosomes in the GnomAD database, including 6,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1098 hom., cov: 31)
  • Exomes 𝑓: 0.079 (5346 hom.)
• Consequence: DIS3L2 NM_152383.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0330
• Publications: 11 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-232087576-A-G is Benign according to our data. Variant chr2-232087576-A-G is described in ClinVar as Benign. ClinVar VariationId is 262632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.033 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

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.456A>G	p.Gln152Gln	synonymous	Exon 6 of 21	NP_689596.4
	DIS3L2	NM_001257281.2		c.456A>G	p.Gln152Gln	synonymous	Exon 6 of 14	NP_001244210.1	Q8IYB7-3
	DIS3L2	NM_001257282.2		c.456A>G	p.Gln152Gln	synonymous	Exon 6 of 7	NP_001244211.1	Q8IYB7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIS3L2	ENST00000325385.12	TSL:5 MANE Select	c.456A>G	p.Gln152Gln	synonymous	Exon 6 of 21	ENSP00000315569.7	Q8IYB7-1
	DIS3L2	ENST00000409401.7	TSL:1	c.456A>G	p.Gln152Gln	synonymous	Exon 6 of 7	ENSP00000386594.3	Q8IYB7-4
	DIS3L2	ENST00000390005.9	TSL:1	n.456A>G		non_coding_transcript_exon	Exon 6 of 21	ENSP00000374655.5	Q8IYB7-2

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16473 AN: 151940 Hom.: 1094 Cov.: 31

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.0370

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0700

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0708

Gnomad OTH AF: 0.101

GnomAD2 exomes AF: 0.0954 AC: 23805 AN: 249446 AF XY: 0.0915

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.165

Gnomad ASJ exome AF: 0.0987

Gnomad EAS exome AF: 0.0357

Gnomad FIN exome AF: 0.0645

Gnomad NFE exome AF: 0.0729

Gnomad OTH exome AF: 0.0848

GnomAD4 exome AF: 0.0790 AC: 115504 AN: 1461770 Hom.: 5346 Cov.: 32 AF XY: 0.0789 AC XY: 57387 AN XY: 727180

African (AFR) AF: 0.194 AC: 6485 AN: 33476

American (AMR) AF: 0.163 AC: 7282 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0963 AC: 2516 AN: 26136

East Asian (EAS) AF: 0.0340 AC: 1348 AN: 39696

South Asian (SAS) AF: 0.107 AC: 9226 AN: 86244

European-Finnish (FIN) AF: 0.0685 AC: 3658 AN: 53416

Middle Eastern (MID) AF: 0.0766 AC: 442 AN: 5768

European-Non Finnish (NFE) AF: 0.0714 AC: 79411 AN: 1111928

Other (OTH) AF: 0.0850 AC: 5136 AN: 60390

GnomAD4 genome AF: 0.109 AC: 16499 AN: 152056 Hom.: 1098 Cov.: 31 AF XY: 0.107 AC XY: 7979 AN XY: 74348

African (AFR) AF: 0.187 AC: 7752 AN: 41444

American (AMR) AF: 0.114 AC: 1748 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0963 AC: 334 AN: 3470

East Asian (EAS) AF: 0.0363 AC: 188 AN: 5182

South Asian (SAS) AF: 0.106 AC: 512 AN: 4822

European-Finnish (FIN) AF: 0.0700 AC: 741 AN: 10590

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0708 AC: 4815 AN: 67966

Other (OTH) AF: 0.105 AC: 222 AN: 2110

Alfa AF: 0.0894 Hom.: 566

Bravo AF: 0.116

Asia WGS AF: 0.100 AC: 348 AN: 3478

EpiCase AF: 0.0697

EpiControl AF: 0.0668

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	Perlman syndrome (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.99
DANN	Benign	0.39
PhyloP100		0.033
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs11887184; hg19: chr2-232952286; COSMIC: COSV108017957; COSMIC: COSV108017957;