rs7852487

Variant names:

• chr9-130696200-T-C
• rs7852487
• NM_014285.7:c.224+607T>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.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
• Publications: 3 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 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.224+607T>C		intron	N/A	NP_055100.2
	EXOSC2	NM_001282708.1		c.224+607T>C		intron	N/A	NP_001269637.1
	EXOSC2	NM_001282709.1		c.224+607T>C		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.224+607T>C		intron	N/A	ENSP00000361433.5
	EXOSC2	ENST00000495699.3	TSL:3	c.224+607T>C		intron	N/A	ENSP00000418463.3
	EXOSC2	ENST00000372352.7	TSL:5	c.224+607T>C		intron	N/A	ENSP00000361427.3

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

African (AFR) AF: 0.110 AC: 4563 AN: 41532

American (AMR) AF: 0.0273 AC: 418 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 67 AN: 3470

East Asian (EAS) AF: 0.0114 AC: 59 AN: 5186

South Asian (SAS) AF: 0.00933 AC: 45 AN: 4824

European-Finnish (FIN) AF: 0.0191 AC: 203 AN: 10608

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0214 AC: 1454 AN: 68014

Other (OTH) AF: 0.0341 AC: 72 AN: 2110

Alfa AF: 0.0293 Hom.: 385

Bravo AF: 0.0489

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.77
PhyloP100		0.46
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: rs7852487; hg19: chr9-133571587;