Variant 9-130693851-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7

The NM_014285.7(EXOSC2):c.60C>A(p.Arg20Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000315 in 1,460,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

EXOSC2
NM_014285.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.321

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 links:

EXOSC2 (HGNC:):

EXOSC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 9-130693851-C-A is Benign according to our data. Variant chr9-130693851-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1903868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.321 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOSC2	NM_014285.7 linkuse as main transcript	c.60C>A	p.Arg20Arg	synonymous_variant	1/9	ENST00000372358.10	NP_055100.2	Q13868-1
EXOSC2	NM_001282708.1 linkuse as main transcript	c.60C>A	p.Arg20Arg	synonymous_variant	1/8		NP_001269637.1	Q13868-2
EXOSC2	NM_001282709.1 linkuse as main transcript	c.60C>A	p.Arg20Arg	synonymous_variant	1/8		NP_001269638.1	Q13868-3
EXOSC2	NR_104230.1 linkuse as main transcript	n.92C>A		non_coding_transcript_exon_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOSC2	ENST00000372358.10 linkuse as main transcript	c.60C>A	p.Arg20Arg	synonymous_variant	1/9	1	NM_014285.7	ENSP00000361433.5		Q13868-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250556

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135584

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000315

AC:

AN:

1460248

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

726454

show subpopulations

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:

0.0000405

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	EXOSC2: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 10, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

8.5

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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