9-130697297-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014285.7(EXOSC2):​c.225-285G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

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>C		intron	N/A	NP_055100.2
	EXOSC2	NM_001282708.1		c.225-285G>C		intron	N/A	NP_001269637.1
	EXOSC2	NM_001282709.1		c.225-285G>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.225-285G>C		intron	N/A	ENSP00000361433.5
	EXOSC2	ENST00000495699.3	TSL:3	c.225-285G>C		intron	N/A	ENSP00000418463.3
	EXOSC2	ENST00000372352.7	TSL:5	c.225-285G>C		intron	N/A	ENSP00000361427.3

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 23048

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0010
DANN	Benign	0.60
PhyloP100		-2.7

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: rs2269337; hg19: chr9-133572684;