9-92474742-C-CTCATCATCATCA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001193335.3(ASPN):c.155_156insTGATGATGATGA(p.Asp48_Asp51dup) variant causes a inframe insertion change. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0071 (5 hom., cov: 0)
  • Exomes 𝑓: 0.0082 (34 hom.)
  • Failed GnomAD Quality Control
• Consequence: ASPN NM_001193335.3 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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 9-92474742-C-CTCATCATCATCA is Benign according to our data. Variant chr9-92474742-C-CTCATCATCATCA is described in ClinVar as [Benign]. Clinvar id is 3033526.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASPN	NM_017680.6	c.155_156insTGATGATGATGA	p.Asp48_Asp51dup	inframe_insertion	2/8	ENST00000710274.1
ASPN	NM_001193335.3	c.155_156insTGATGATGATGA	p.Asp48_Asp51dup	inframe_insertion	2/6
CENPP	NM_001012267.3	c.564+94916_564+94927dup		intron_variant		ENST00000375587.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASPN	ENST00000375544.7	c.155_156insTGATGATGATGA	p.Asp48_Asp51dup	inframe_insertion	2/8	1		P1
CENPP	ENST00000375587.8	c.564+94916_564+94927dup		intron_variant		1	NM_001012267.3	P1

Frequencies

GnomAD3 genomes AF: 0.00711 AC: 1049 AN: 147580 Hom.: 5 Cov.: 0

Gnomad AFR AF: 0.00281

Gnomad AMI AF: 0.00111

Gnomad AMR AF: 0.00620

Gnomad ASJ AF: 0.00350

Gnomad EAS AF: 0.00200

Gnomad SAS AF: 0.00942

Gnomad FIN AF: 0.0147

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.00924

Gnomad OTH AF: 0.00649

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00824 AC: 11423 AN: 1386474 Hom.: 34 Cov.: 0 AF XY: 0.00838 AC XY: 5784 AN XY: 690336

Gnomad4 AFR exome AF: 0.00273

Gnomad4 AMR exome AF: 0.00321

Gnomad4 ASJ exome AF: 0.00293

Gnomad4 EAS exome AF: 0.00119

Gnomad4 SAS exome AF: 0.00977

Gnomad4 FIN exome AF: 0.0133

Gnomad4 NFE exome AF: 0.00868

Gnomad4 OTH exome AF: 0.00718

GnomAD4 genome AF: 0.00709 AC: 1047 AN: 147686 Hom.: 5 Cov.: 0 AF XY: 0.00737 AC XY: 529 AN XY: 71794

Gnomad4 AFR AF: 0.00280

Gnomad4 AMR AF: 0.00620

Gnomad4 ASJ AF: 0.00350

Gnomad4 EAS AF: 0.00200

Gnomad4 SAS AF: 0.00899

Gnomad4 FIN AF: 0.0147

Gnomad4 NFE AF: 0.00925

Gnomad4 OTH AF: 0.00642

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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). -

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;