Genetic Variant DIS3L2:c.*249T>C (chr2-232343824-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001257281.2(DIS3L2):c.*249T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 420,556 control chromosomes in the GnomAD database, including 24,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 14252 hom., cov: 33)

Exomes 𝑓: 0.23 ( 10176 hom. )

Consequence

DIS3L2
NM_001257281.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.80

Variant links:

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 links:

NRBF2P6 (HGNC:54797): (NRBF2 pseudogene 6)

NRBF2P6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 2-232343824-T-C is Benign according to our data. Variant chr2-232343824-T-C is described in ClinVar as [Benign]. Clinvar id is 1281698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIS3L2	NM_001257281.2 link	c.*249T>C		3_prime_UTR_variant	Exon 14 of 14		NP_001244210.1	Q8IYB7-3
NRBF2P6		n.232343824T>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIS3L2	ENST00000273009.10 link	c.*249T>C		3_prime_UTR_variant	Exon 14 of 14	2		ENSP00000273009.6		Q8IYB7-3
NRBF2P6	ENST00000513620.1 link	n.709T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

AF:

0.353

AC:

53635

AN:

152004

Hom.:

14205

Cov.:

show subpopulations

Gnomad AFR

AF:

0.729

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.386

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.497

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.170

Gnomad MID

AF:

0.194

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.311

GnomAD4 exome

AF:

0.229

AC:

61596

AN:

268434

Hom.:

10176

Cov.:

AF XY:

0.222

AC XY:

30910

AN XY:

139276

show subpopulations

Gnomad4 AFR exome

AF:

0.734

Gnomad4 AMR exome

AF:

0.490

Gnomad4 ASJ exome

AF:

0.179

Gnomad4 EAS exome

AF:

0.527

Gnomad4 SAS exome

AF:

0.195

Gnomad4 FIN exome

AF:

0.191

Gnomad4 NFE exome

AF:

0.160

Gnomad4 OTH exome

AF:

0.248

GnomAD4 genome

AF:

0.353

AC:

53749

AN:

152122

Hom.:

14252

Cov.:

AF XY:

0.353

AC XY:

26247

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.729

Gnomad4 AMR

AF:

0.387

Gnomad4 ASJ

AF:

0.173

Gnomad4 EAS

AF:

0.497

Gnomad4 SAS

AF:

0.200

Gnomad4 FIN

AF:

0.170

Gnomad4 NFE

AF:

0.159

Gnomad4 OTH

AF:

0.312

Alfa

AF:

0.277

Hom.:

1233

Bravo

AF:

0.391

Asia WGS

AF:

0.364

AC:

1265

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 02, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.6

DANN

Benign

0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over