Genetic Variant EXOSC2:p.Pro8Thr (chr9-130693813-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P8A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EXOSC2
NM_014285.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.85

Publications

0 publications found

Variant links:

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]

EXOSC2 Gene-Disease associations (from GenCC):

retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

EXOSC2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22699466).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014285.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EXOSC2	NM_014285.7	MANE Select	c.22C>A	p.Pro8Thr	missense	Exon 1 of 9	NP_055100.2
EXOSC2	NM_001282708.1		c.22C>A	p.Pro8Thr	missense	Exon 1 of 8	NP_001269637.1	Q13868-2
EXOSC2	NM_001282709.1		c.22C>A	p.Pro8Thr	missense	Exon 1 of 8	NP_001269638.1	Q13868-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EXOSC2	ENST00000372358.10	TSL:1 MANE Select	c.22C>A	p.Pro8Thr	missense	Exon 1 of 9	ENSP00000361433.5	Q13868-1
EXOSC2	ENST00000851443.1		c.22C>A	p.Pro8Thr	missense	Exon 1 of 10	ENSP00000521502.1
EXOSC2	ENST00000495699.3	TSL:3	c.22C>A	p.Pro8Thr	missense	Exon 1 of 8	ENSP00000418463.3	A3KFL5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1457050

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725028

African (AFR)

AF:

0.00

AC:

AN:

33356

American (AMR)

AF:

0.00

AC:

AN:

44464

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26026

East Asian (EAS)

AF:

0.00

AC:

AN:

39494

South Asian (SAS)

AF:

0.00

AC:

AN:

86100

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52776

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109030

Other (OTH)

AF:

0.00

AC:

AN:

60054

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Benign

0.58

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.010

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.3

PhyloP100

3.9

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.4

REVEL

Benign

0.16

Sift

Uncertain

0.010

Sift4G

Uncertain

0.055

Polyphen

0.98

Vest4

0.48

MutPred

0.38

Loss of helix (P = 0.028)

MVP

0.55

MPC

0.63

ClinPred

0.96

GERP RS

6.1

PromoterAI

0.042

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.73

gMVP

0.72

Mutation Taster

=80/20

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over