rs12988522

Variant names:

• chr2-231974180-G-A
• rs12988522
• NM_152383.5:c.-94+12415G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152383.5(DIS3L2):​c.-94+12415G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,136 control chromosomes in the GnomAD database, including 1,859 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1859 hom., cov: 31)
• Consequence: DIS3L2 NM_152383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.325 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.-94+12415G>A		intron	N/A	NP_689596.4
	DIS3L2	NM_001257281.2		c.-94+12415G>A		intron	N/A	NP_001244210.1	Q8IYB7-3
	DIS3L2	NM_001257282.2		c.-94+12415G>A		intron	N/A	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.-94+12415G>A		intron	N/A	ENSP00000315569.7	Q8IYB7-1
	DIS3L2	ENST00000409401.7	TSL:1	c.-94+12415G>A		intron	N/A	ENSP00000386594.3	Q8IYB7-4
	DIS3L2	ENST00000390005.9	TSL:1	n.-94+12415G>A		intron	N/A	ENSP00000374655.5	Q8IYB7-2

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20350 AN: 152016 Hom.: 1855 Cov.: 31

Gnomad AFR AF: 0.0346

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.0983

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.171

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.134 AC: 20355 AN: 152136 Hom.: 1859 Cov.: 31 AF XY: 0.135 AC XY: 10024 AN XY: 74376

African (AFR) AF: 0.0345 AC: 1433 AN: 41510

American (AMR) AF: 0.141 AC: 2145 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 774 AN: 3472

East Asian (EAS) AF: 0.260 AC: 1343 AN: 5174

South Asian (SAS) AF: 0.339 AC: 1630 AN: 4808

European-Finnish (FIN) AF: 0.0983 AC: 1043 AN: 10606

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11504 AN: 67996

Other (OTH) AF: 0.175 AC: 370 AN: 2110

Alfa AF: 0.168 Hom.: 7237

Bravo AF: 0.130

Asia WGS AF: 0.342 AC: 1185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.68
PhyloP100		0.070
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: rs12988522; hg19: chr2-232838890;