9-130693851-C-A

Variant names:

• chr9-130693851-C-A
• rs963425075
• NM_014285.7:c.60C>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2 BP4_Moderate BP6_Very_Strong BP7

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.321
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOSC2	NM_014285.7	MANE Select	c.60C>A	p.Arg20Arg	synonymous	Exon 1 of 9	NP_055100.2
	EXOSC2	NM_001282708.1		c.60C>A	p.Arg20Arg	synonymous	Exon 1 of 8	NP_001269637.1	Q13868-2
	EXOSC2	NM_001282709.1		c.60C>A	p.Arg20Arg	synonymous	Exon 1 of 8	NP_001269638.1	Q13868-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOSC2	ENST00000372358.10	TSL:1 MANE Select	c.60C>A	p.Arg20Arg	synonymous	Exon 1 of 9	ENSP00000361433.5	Q13868-1
	EXOSC2	ENST00000851443.1		c.60C>A	p.Arg20Arg	synonymous	Exon 1 of 10	ENSP00000521502.1
	EXOSC2	ENST00000495699.3	TSL:3	c.60C>A	p.Arg20Arg	synonymous	Exon 1 of 8	ENSP00000418463.3	A3KFL5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250556 AF XY: 0.00000738

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000315 AC: 46 AN: 1460248 Hom.: 0 Cov.: 33 AF XY: 0.0000303 AC XY: 22 AN XY: 726454

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39610

South Asian (SAS) AF: 0.00 AC: 0 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000405 AC: 45 AN: 1110888

Other (OTH) AF: 0.0000166 AC: 1 AN: 60258

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	8.5
DANN	Benign	0.74
PhyloP100		-0.32
PromoterAI		-0.095	Neutral
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

Other links and lift over

dbSNP: rs963425075; hg19: chr9-133569238;