rs2269337

Variant names:

• chr9-130697297-G-A
• rs2269337
• NM_014285.7:c.225-285G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-130697297-G-A
• chr9-130697297-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014285.7(EXOSC2):​c.225-285G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,084 control chromosomes in the GnomAD database, including 12,921 homozygotes. 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: 𝑓 0.35 (12921 hom., cov: 33)
• Consequence: EXOSC2 NM_014285.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74
• Publications: 9 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ENSG00000306514 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOSC2	NM_014285.7	MANE Select	c.225-285G>A		intron	N/A	NP_055100.2
	EXOSC2	NM_001282708.1		c.225-285G>A		intron	N/A	NP_001269637.1
	EXOSC2	NM_001282709.1		c.225-285G>A		intron	N/A	NP_001269638.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOSC2	ENST00000372358.10	TSL:1 MANE Select	c.225-285G>A		intron	N/A	ENSP00000361433.5
	EXOSC2	ENST00000495699.3	TSL:3	c.225-285G>A		intron	N/A	ENSP00000418463.3
	EXOSC2	ENST00000372352.7	TSL:5	c.225-285G>A		intron	N/A	ENSP00000361427.3

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53644 AN: 151966 Hom.: 12880 Cov.: 33

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.319

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.353 AC: 53747 AN: 152084 Hom.: 12921 Cov.: 33 AF XY: 0.356 AC XY: 26470 AN XY: 74350

African (AFR) AF: 0.667 AC: 27673 AN: 41464

American (AMR) AF: 0.360 AC: 5499 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 644 AN: 3470

East Asian (EAS) AF: 0.541 AC: 2794 AN: 5160

South Asian (SAS) AF: 0.324 AC: 1561 AN: 4822

European-Finnish (FIN) AF: 0.234 AC: 2468 AN: 10562

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12295 AN: 68000

Other (OTH) AF: 0.326 AC: 689 AN: 2114

Alfa AF: 0.231 Hom.: 23048

Bravo AF: 0.378

Asia WGS AF: 0.444 AC: 1543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0010
DANN	Benign	0.74
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs2269337; hg19: chr9-133572684;