rs4973500

Variant names:

• chr2-232030738-G-A
• rs4973500
• NM_152383.5:c.366+658G>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.366+658G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,144 control chromosomes in the GnomAD database, including 1,873 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 0.14 (1873 hom., cov: 32)
• Consequence: DIS3L2 NM_152383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIS3L2	NM_152383.5	c.366+658G>A		intron_variant	Intron 5 of 20	ENST00000325385.12	NP_689596.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIS3L2	ENST00000325385.12	c.366+658G>A		intron_variant	Intron 5 of 20	5	NM_152383.5	ENSP00000315569.7

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20986 AN: 152026 Hom.: 1869 Cov.: 32

Gnomad AFR AF: 0.0493

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.0985

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.138 AC: 20993 AN: 152144 Hom.: 1873 Cov.: 32 AF XY: 0.139 AC XY: 10322 AN XY: 74380

African (AFR) AF: 0.0492 AC: 2042 AN: 41536

American (AMR) AF: 0.144 AC: 2196 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 769 AN: 3458

East Asian (EAS) AF: 0.261 AC: 1346 AN: 5162

South Asian (SAS) AF: 0.338 AC: 1630 AN: 4820

European-Finnish (FIN) AF: 0.0985 AC: 1043 AN: 10594

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11469 AN: 67986

Other (OTH) AF: 0.181 AC: 383 AN: 2114

Alfa AF: 0.142 Hom.: 339

Bravo AF: 0.134

Asia WGS AF: 0.342 AC: 1183 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.9
DANN	Benign	0.69
PhyloP100		1.2
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: rs4973500; hg19: chr2-232895448;