rs2296666

Variant names:

• chr9-92511979-A-G
• rs2296666
• NM_001393.4:c.1170+32T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

Genes affected

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]

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECM2	NM_001393.4	MANE Select	c.1170+32T>C		intron	N/A	NP_001384.1
	CENPP	NM_001012267.3	MANE Select	c.565-99335A>G		intron	N/A	NP_001012267.1
	ECM2	NM_001197295.2		c.1104+32T>C		intron	N/A	NP_001184224.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECM2	ENST00000344604.10	TSL:1 MANE Select	c.1170+32T>C		intron	N/A	ENSP00000344758.5
	CENPP	ENST00000375587.8	TSL:1 MANE Select	c.565-99335A>G		intron	N/A	ENSP00000364737.3
	ECM2	ENST00000444490.6	TSL:1	c.1104+32T>C		intron	N/A	ENSP00000393971.2

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

GnomAD2 exomes AF: 0.296 AC: 66890 AN: 225822 AF XY: 0.293

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 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

African (AFR) AF: 0.656 AC: 19345 AN: 29488

American (AMR) AF: 0.208 AC: 8389 AN: 40388

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 9594 AN: 24204

East Asian (EAS) AF: 0.191 AC: 7227 AN: 37918

South Asian (SAS) AF: 0.219 AC: 17071 AN: 77780

European-Finnish (FIN) AF: 0.267 AC: 13912 AN: 52046

Middle Eastern (MID) AF: 0.385 AC: 2103 AN: 5464

European-Non Finnish (NFE) AF: 0.316 AC: 327212 AN: 1034836

Other (OTH) AF: 0.318 AC: 17976 AN: 56512

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

African (AFR) AF: 0.645 AC: 26741 AN: 41478

American (AMR) AF: 0.297 AC: 4547 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1414 AN: 3472

East Asian (EAS) AF: 0.146 AC: 755 AN: 5176

South Asian (SAS) AF: 0.232 AC: 1119 AN: 4824

European-Finnish (FIN) AF: 0.268 AC: 2841 AN: 10582

Middle Eastern (MID) AF: 0.521 AC: 151 AN: 290

European-Non Finnish (NFE) AF: 0.331 AC: 22476 AN: 67982

Other (OTH) AF: 0.404 AC: 852 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.17
DANN	Benign	0.87
PhyloP100		0.067
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2296666; hg19: chr9-95274261;