9-92474742-C-CTCA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001193335.3(ASPN):c.155_156insTGA(p.Asp51dup) variant causes a inframe insertion change. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6793 hom., cov: 0)
  • Exomes 𝑓: 0.19 (13869 hom.)
• Consequence: ASPN NM_001193335.3 inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:2
• 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 -16 ACMG points.

• BP6: Variant 9-92474742-C-CTCA is Benign according to our data. Variant chr9-92474742-C-CTCA is described in ClinVar as [Benign]. Clinvar id is 2527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASPN	NM_017680.6	c.155_156insTGA	p.Asp51dup	inframe_insertion	2/8	ENST00000710274.1
ASPN	NM_001193335.3	c.155_156insTGA	p.Asp51dup	inframe_insertion	2/6
CENPP	NM_001012267.3	c.564+94925_564+94927dup		intron_variant		ENST00000375587.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASPN	ENST00000375544.7	c.155_156insTGA	p.Asp51dup	inframe_insertion	2/8	1		P1
CENPP	ENST00000375587.8	c.564+94925_564+94927dup		intron_variant		1	NM_001012267.3	P1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 39967 AN: 147386 Hom.: 6790 Cov.: 0

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.0332

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.249

GnomAD4 exome AF: 0.192 AC: 265438 AN: 1383238 Hom.: 13869 Cov.: 0 AF XY: 0.191 AC XY: 131736 AN XY: 688804

Gnomad4 AFR exome AF: 0.419

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.251

Gnomad4 EAS exome AF: 0.0380

Gnomad4 SAS exome AF: 0.162

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.194

Gnomad4 OTH exome AF: 0.208

GnomAD4 genome AF: 0.271 AC: 39995 AN: 147490 Hom.: 6793 Cov.: 0 AF XY: 0.265 AC XY: 18973 AN XY: 71698

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.0335

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.247

ClinVar

Significance: Benign

Submissions summary: Benign:2 Other:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital

Mar 19, 2020

- -

CENPP-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Osteoarthritis susceptibility 3 Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 01, 2008

- -

Lumbar disk degeneration, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 01, 2008

- -

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;