9-92494237-C-T

Position:

• chr9-92494237-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012267.3(CENPP):​c.564+114378C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 1,354,886 control chromosomes in the GnomAD database, including 174,325 homozygotes. 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: 𝑓 0.41 (15557 hom., cov: 32)
  • Exomes 𝑓: 0.51 (158768 hom.)
• Consequence: CENPP NM_001012267.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272

Genes affected

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]

ECM2 (HGNC:3154): (extracellular matrix protein 2) ECM2 encodes extracellular matrix protein 2, so named because it shares extensive similarity with known extracelluar matrix proteins. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPP	NM_001012267.3	c.564+114378C>T		intron_variant		ENST00000375587.8	NP_001012267.1
ECM2	NM_001197296.2	c.1866-88G>A		intron_variant			NP_001184225.1
CENPP	NM_001286969.1	c.228+114378C>T		intron_variant			NP_001273898.1
CENPP	XM_024447543.2	c.288+114378C>T		intron_variant			XP_024303311.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPP	ENST00000375587.8	c.564+114378C>T		intron_variant		1	NM_001012267.3	ENSP00000364737	P1
ECM2	ENST00000444490.6	c.1866-88G>A		intron_variant		1		ENSP00000393971

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62794 AN: 151964 Hom.: 15550 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.431

GnomAD4 exome AF: 0.506 AC: 608160 AN: 1202804 Hom.: 158768 AF XY: 0.504 AC XY: 303750 AN XY: 602228

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.576

Gnomad4 ASJ exome AF: 0.463

Gnomad4 EAS exome AF: 0.757

Gnomad4 SAS exome AF: 0.475

Gnomad4 FIN exome AF: 0.549

Gnomad4 NFE exome AF: 0.507

Gnomad4 OTH exome AF: 0.502

GnomAD4 genome AF: 0.413 AC: 62803 AN: 152082 Hom.: 15557 Cov.: 32 AF XY: 0.420 AC XY: 31191 AN XY: 74330

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.798

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.437

Alfa AF: 0.484 Hom.: 24885

Bravo AF: 0.400

Asia WGS AF: 0.600 AC: 2088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.2
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs331380; hg19: chr9-95256519; COSMIC: COSV60739057; COSMIC: COSV60739057;