rs2269337

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOSC2	NM_014285.7	c.225-285G>A		intron_variant		ENST00000372358.10	NP_055100.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOSC2	ENST00000372358.10	c.225-285G>A		intron_variant		1	NM_014285.7	ENSP00000361433.5

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

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.541

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.326

Alfa AF: 0.200 Hom.: 7324

Bravo AF: 0.378

Asia WGS AF: 0.444 AC: 1543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0010
DANN	Benign	0.74

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

Other links and lift over

dbSNP: rs2269337; hg19: chr9-133572684;