rs780625125

Variant names:

• chr2-232334417-C-A
• NM_152383.5:c.2207C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-232334417-C-A
• chr2-232334417-C-G
• chr2-232334417-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152383.5(DIS3L2):​c.2207C>A​(p.Ala736Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,462 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DIS3L2 NM_152383.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.58

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIS3L2	NM_152383.5	c.2207C>A	p.Ala736Glu	missense_variant	Exon 18 of 21	ENST00000325385.12	NP_689596.4
DIS3L2	NM_001257281.2	c.1582-8928C>A		intron_variant	Intron 13 of 13		NP_001244210.1
DIS3L2	NR_046476.2	n.2280C>A		non_coding_transcript_exon_variant	Exon 18 of 21
DIS3L2	NR_046477.2	n.2259C>A		non_coding_transcript_exon_variant	Exon 17 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIS3L2	ENST00000325385.12	c.2207C>A	p.Ala736Glu	missense_variant	Exon 18 of 21	5	NM_152383.5	ENSP00000315569.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461462 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727046

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T;T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;.;D
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.73	D;D;D
MetaSVM	Benign	-0.29	T
MutationAssessor	Pathogenic	3.2	M;M;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.011	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.95
MutPred		0.55		Gain of disorder (P = 0.0627);Gain of disorder (P = 0.0627);.;
MVP		0.30
MPC		0.89
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.66
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-233199127;