9-92474742-CTCATCATCA-C

Position:

• chr9-92474742-CTCATCATCA-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000375544.7(ASPN):​c.147_155del​(p.Asp49_Asp51del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00038 in 1,533,548 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00038 (1 hom.)
• Consequence: ASPN ENST00000375544.7 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.52

Genes affected

ASPN (HGNC:14872): (asporin) This gene encodes a cartilage extracellular protein that is member of the small leucine-rich proteoglycan family. The encoded protein may regulate chondrogenesis by inhibiting transforming growth factor-beta 1-induced gene expression in cartilage. This protein also binds collagen and calcium and may induce collagen mineralization. Polymorphisms in the aspartic acid repeat region of this gene are associated with a susceptibility to osteoarthritis, and also with intervertebral disc disease. Alternative splicing of this gene results in multiple transcript variants.[provided by RefSeq, Jul 2014]

CENPP (HGNC:32933): (centromere protein P) CENPP is a subunit of a CENPH (MIM 605607)-CENPI (MIM 300065)-associated centromeric complex that targets CENPA (MIM 117139) to centromeres and is required for proper kinetochore function and mitotic progression (Okada et al., 2006 [PubMed 16622420]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASPN	NM_017680.6	c.147_155del	p.Asp49_Asp51del	inframe_deletion	2/8	ENST00000710274.1
ASPN	NM_001193335.3	c.147_155del	p.Asp49_Asp51del	inframe_deletion	2/6
CENPP	NM_001012267.3	c.564+94919_564+94927del		intron_variant		ENST00000375587.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASPN	ENST00000375544.7	c.147_155del	p.Asp49_Asp51del	inframe_deletion	2/8	1		P1
CENPP	ENST00000375587.8	c.564+94919_564+94927del		intron_variant		1	NM_001012267.3	P1

Frequencies

GnomAD3 genomes AF: 0.000346 AC: 51 AN: 147582 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000329

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000136

Gnomad ASJ AF: 0.000874

Gnomad EAS AF: 0.000600

Gnomad SAS AF: 0.000219

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000432

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000384 AC: 532 AN: 1385966 Hom.: 1 AF XY: 0.000368 AC XY: 254 AN XY: 690112

Gnomad4 AFR exome AF: 0.000716

Gnomad4 AMR exome AF: 0.000390

Gnomad4 ASJ exome AF: 0.000724

Gnomad4 EAS exome AF: 0.000400

Gnomad4 SAS exome AF: 0.000307

Gnomad4 FIN exome AF: 0.0000792

Gnomad4 NFE exome AF: 0.000390

Gnomad4 OTH exome AF: 0.000313

GnomAD4 genome AF: 0.000346 AC: 51 AN: 147582 Hom.: 0 Cov.: 0 AF XY: 0.000181 AC XY: 13 AN XY: 71678

Gnomad4 AFR AF: 0.000329

Gnomad4 AMR AF: 0.000136

Gnomad4 ASJ AF: 0.000874

Gnomad4 EAS AF: 0.000600

Gnomad4 SAS AF: 0.000219

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000432

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3078372; hg19: chr9-95237024;