2-232123872-A-C

Variant names:

• chr2-232123872-A-C
• rs3103267
• NM_152383.5:c.602-6747A>C

Variant summary

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

The NM_152383.5(DIS3L2):​c.602-6747A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 152,034 control chromosomes in the GnomAD database, including 38,916 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 0.70 (38916 hom., cov: 31)
• Consequence: DIS3L2 NM_152383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.522
• Publications: 12 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIS3L2	NM_152383.5	c.602-6747A>C		intron_variant	Intron 6 of 20	ENST00000325385.12	NP_689596.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIS3L2	ENST00000325385.12	c.602-6747A>C		intron_variant	Intron 6 of 20	5	NM_152383.5	ENSP00000315569.7

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107073 AN: 151916 Hom.: 38872 Cov.: 31

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.705 AC: 107166 AN: 152034 Hom.: 38916 Cov.: 31 AF XY: 0.699 AC XY: 51947 AN XY: 74278

African (AFR) AF: 0.793 AC: 32896 AN: 41470

American (AMR) AF: 0.614 AC: 9381 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2206 AN: 3466

East Asian (EAS) AF: 0.221 AC: 1143 AN: 5164

South Asian (SAS) AF: 0.460 AC: 2217 AN: 4818

European-Finnish (FIN) AF: 0.805 AC: 8500 AN: 10558

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48569 AN: 67968

Other (OTH) AF: 0.655 AC: 1382 AN: 2110

Alfa AF: 0.704 Hom.: 67723

Bravo AF: 0.696

Asia WGS AF: 0.371 AC: 1294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.61
DANN	Benign	0.78
PhyloP100		-0.52
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: rs3103267; hg19: chr2-232988582;