rs148203698

Variant names:

• chr9-130693813-C-A
• NM_014285.7:c.22C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-130693813-C-A
• chr9-130693813-C-G
• chr9-130693813-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014285.7(EXOSC2):​c.22C>A​(p.Pro8Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EXOSC2 NM_014285.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.85

Genes affected

EXOSC2 (HGNC:17097): (exosome component 2) Predicted to enable RNA binding activity. Involved in positive regulation of cell growth. Located in cytoplasm; nucleolus; and nucleoplasm. Part of nuclear exosome (RNase complex). [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22699466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOSC2	NM_014285.7	c.22C>A	p.Pro8Thr	missense_variant	Exon 1 of 9	ENST00000372358.10	NP_055100.2
EXOSC2	NM_001282708.1	c.22C>A	p.Pro8Thr	missense_variant	Exon 1 of 8		NP_001269637.1
EXOSC2	NM_001282709.1	c.22C>A	p.Pro8Thr	missense_variant	Exon 1 of 8		NP_001269638.1
EXOSC2	NR_104230.1	n.54C>A		non_coding_transcript_exon_variant	Exon 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOSC2	ENST00000372358.10	c.22C>A	p.Pro8Thr	missense_variant	Exon 1 of 9	1	NM_014285.7	ENSP00000361433.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1457050 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 725028

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T;.;T;.;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Benign	0.58	D
LIST_S2	Uncertain	0.91	D;D;D;D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.23	T;T;T;T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.3	M;M;.;M;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.4	N;N;N;N;N
REVEL	Benign	0.16
Sift	Uncertain	0.010	D;D;D;D;D
Sift4G	Uncertain	0.055	T;D;T;D;D
Polyphen		0.98	D;.;.;.;.
Vest4		0.48
MutPred		0.38		Loss of helix (P = 0.028);Loss of helix (P = 0.028);Loss of helix (P = 0.028);Loss of helix (P = 0.028);Loss of helix (P = 0.028);
MVP		0.55
MPC		0.63
ClinPred		0.96	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.73
gMVP		0.72

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-133569200;