rs7852487

Positions:

• chr9-130696200-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014285.7(EXOSC2):​c.224+607T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0452 in 152,238 control chromosomes in the GnomAD database, including 259 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 0.045 (259 hom., cov: 31)
• Consequence: EXOSC2 NM_014285.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.460

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOSC2	NM_014285.7	c.224+607T>C		intron_variant		ENST00000372358.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOSC2	ENST00000372358.10	c.224+607T>C		intron_variant		1	NM_014285.7	P1

Frequencies

GnomAD3 genomes AF: 0.0452 AC: 6870 AN: 152120 Hom.: 256 Cov.: 31

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0274

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.0114

Gnomad SAS AF: 0.00932

Gnomad FIN AF: 0.0191

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0214

Gnomad OTH AF: 0.0345

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

GnomAD4 genome AF: 0.0452 AC: 6885 AN: 152238 Hom.: 259 Cov.: 31 AF XY: 0.0444 AC XY: 3306 AN XY: 74436

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.0273

Gnomad4 ASJ AF: 0.0193

Gnomad4 EAS AF: 0.0114

Gnomad4 SAS AF: 0.00933

Gnomad4 FIN AF: 0.0191

Gnomad4 NFE AF: 0.0214

Gnomad4 OTH AF: 0.0341

Alfa AF: 0.0248 Hom.: 91

Bravo AF: 0.0489

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.77

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: rs7852487; hg19: chr9-133571587;