2-232343267-C-A

Variant names:

• chr2-232343267-C-A
• rs1125045
• NM_001257281.2:c.1582-78C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001257281.2(DIS3L2):​c.1582-78C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000902 in 1,108,464 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
• Consequence: DIS3L2 NM_001257281.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.59
• Publications: 0 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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257281.2. 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_001257281.2		c.1582-78C>A		intron	N/A	NP_001244210.1	Q8IYB7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIS3L2	ENST00000273009.10	TSL:2	c.1582-78C>A		intron	N/A	ENSP00000273009.6	Q8IYB7-3
	NRBF2P6	ENST00000513620.1	TSL:6	n.152C>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.02e-7 AC: 1 AN: 1108464 Hom.: 0 Cov.: 15 AF XY: 0.00000182 AC XY: 1 AN XY: 550804

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24754

American (AMR) AF: 0.00 AC: 0 AN: 27654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19208

East Asian (EAS) AF: 0.00 AC: 0 AN: 35872

South Asian (SAS) AF: 0.00 AC: 0 AN: 63548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3494

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 838764

Other (OTH) AF: 0.00 AC: 0 AN: 47656

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.9
DANN	Benign	0.49
PhyloP100		2.6

Splicing

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

Other links and lift over

dbSNP: rs1125045; hg19: chr2-233207977;