9-92474742-C-CTCATCA

Variant names:

• chr9-92474742-C-CTCATCA
• rs3078372
• ENST00000375544.7:c.150_155dupTGATGA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_017680.6(ASPN):​c.150_155dupTGATGA​(p.Asp50_Asp51dup) variant causes a disruptive inframe insertion change. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.073 (444 hom., cov: 0)
  • Exomes 𝑓: 0.073 (2003 hom.)
• Consequence: ASPN NM_017680.6 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 Benign. Variant got -10 ACMG points.

• BP6: Variant 9-92474742-C-CTCATCA is Benign according to our data. Variant chr9-92474742-C-CTCATCA is described in ClinVar as [Benign]. Clinvar id is 1237100.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPP	NM_001012267.3	c.564+94922_564+94927dupATCATC		intron_variant	Intron 5 of 7	ENST00000375587.8	NP_001012267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASPN	ENST00000375544.7	c.150_155dupTGATGA	p.Asp50_Asp51dup	disruptive_inframe_insertion	Exon 2 of 8	1		ENSP00000364694.3
CENPP	ENST00000375587.8	c.564+94922_564+94927dupATCATC		intron_variant	Intron 5 of 7	1	NM_001012267.3	ENSP00000364737.3

Frequencies

GnomAD3 genomes AF: 0.0727 AC: 10723 AN: 147504 Hom.: 444 Cov.: 0

Gnomad AFR AF: 0.0804

Gnomad AMI AF: 0.0490

Gnomad AMR AF: 0.0654

Gnomad ASJ AF: 0.0717

Gnomad EAS AF: 0.0502

Gnomad SAS AF: 0.0280

Gnomad FIN AF: 0.0673

Gnomad MID AF: 0.0645

Gnomad NFE AF: 0.0756

Gnomad OTH AF: 0.0744

GnomAD4 exome AF: 0.0728 AC: 100838 AN: 1385086 Hom.: 2003 Cov.: 0 AF XY: 0.0713 AC XY: 49141 AN XY: 689672

Gnomad4 AFR exome AF: 0.0844

Gnomad4 AMR exome AF: 0.0625

Gnomad4 ASJ exome AF: 0.0683

Gnomad4 EAS exome AF: 0.0700

Gnomad4 SAS exome AF: 0.0259

Gnomad4 FIN exome AF: 0.0668

Gnomad4 NFE exome AF: 0.0775

Gnomad4 OTH exome AF: 0.0647

GnomAD4 genome AF: 0.0727 AC: 10735 AN: 147610 Hom.: 444 Cov.: 0 AF XY: 0.0717 AC XY: 5144 AN XY: 71758

Gnomad4 AFR AF: 0.0804

Gnomad4 AMR AF: 0.0654

Gnomad4 ASJ AF: 0.0717

Gnomad4 EAS AF: 0.0505

Gnomad4 SAS AF: 0.0278

Gnomad4 FIN AF: 0.0673

Gnomad4 NFE AF: 0.0757

Gnomad4 OTH AF: 0.0726

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Reported in 3.1% of alleles of patients with developmental hip dysplasia in the Han Chinese population, but also seen in 3.4% of alleles of control samples, which was not a statistically significant difference (Shi et al., 2011); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; The D15 allele is described as a possible risk allele associated with knee osteoarthritis in the Greek population however, this finding was not statistically significant (Kaliakatsos et al., 2006); Among Han Chinese patients with ankylosing spondylitis the frequency of the D15 allele was the same as in controls (Liu et al., 2010); In-frame duplication of 2 Aspartate residues, which results in an allele with 15 Aspartate residues, or a D15 allele; This variant is associated with the following publications: (PMID: 21329514, 16377215, 20144272, 29233086) -

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;