rs2296666

chr9-92511979-A-G

Variant summary

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

The NM_001393.4(ECM2):c.1170+32T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 1,510,748 control chromosomes in the GnomAD database, including 83,655 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 0.40 (14425 hom., cov: 32)
  • Exomes 𝑓: 0.31 (69230 hom.)
• Consequence: ECM2 NM_001393.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPP	NM_001012267.3	c.565-99335A>G		intron_variant		ENST00000375587.8
ECM2	NM_001393.4	c.1170+32T>C		intron_variant		ENST00000344604.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECM2	ENST00000344604.10	c.1170+32T>C		intron_variant		1	NM_001393.4	P1
CENPP	ENST00000375587.8	c.565-99335A>G		intron_variant		1	NM_001012267.3	P1
ECM2	ENST00000444490.6	c.1104+32T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61375 AN: 151994 Hom.: 14402 Cov.: 32

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.408

GnomAD3 exomes AF: 0.296 AC: 66890 AN: 225822 Hom.: 11494 AF XY: 0.293 AC XY: 35829 AN XY: 122336

Gnomad AFR exome AF: 0.653

Gnomad AMR exome AF: 0.194

Gnomad ASJ exome AF: 0.384

Gnomad EAS exome AF: 0.124

Gnomad SAS exome AF: 0.217

Gnomad FIN exome AF: 0.264

Gnomad NFE exome AF: 0.323

Gnomad OTH exome AF: 0.305

GnomAD4 exome AF: 0.311 AC: 422829 AN: 1358636 Hom.: 69230 Cov.: 18 AF XY: 0.309 AC XY: 209800 AN XY: 678076

Gnomad4 AFR exome AF: 0.656

Gnomad4 AMR exome AF: 0.208

Gnomad4 ASJ exome AF: 0.396

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.219

Gnomad4 FIN exome AF: 0.267

Gnomad4 NFE exome AF: 0.316

Gnomad4 OTH exome AF: 0.318

GnomAD4 genome AF: 0.404 AC: 61439 AN: 152112 Hom.: 14425 Cov.: 32 AF XY: 0.394 AC XY: 29332 AN XY: 74362

Gnomad4 AFR AF: 0.645

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.404

Alfa AF: 0.371 Hom.: 3103

Bravo AF: 0.419

Asia WGS AF: 0.235 AC: 818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	0.17
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2296666; hg19: chr9-95274261;