9-92528174-G-A

Position:

• chr9-92528174-G-A

Variant summary

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

The NM_001393.4(ECM2):​c.-27-5281C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 152,068 control chromosomes in the GnomAD database, including 15,617 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 0.42 (15602 hom., cov: 31)
  • Exomes 𝑓: 0.37 (15 hom.)
• Consequence: ECM2 NM_001393.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.544

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]

ECM2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECM2	NM_001393.4	c.-27-5281C>T		intron_variant		ENST00000344604.10	NP_001384.1
CENPP	NM_001012267.3	c.565-83140G>A		intron_variant		ENST00000375587.8	NP_001012267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECM2	ENST00000344604.10	c.-27-5281C>T		intron_variant		1	NM_001393.4	ENSP00000344758.5
CENPP	ENST00000375587.8	c.565-83140G>A		intron_variant		1	NM_001012267.3	ENSP00000364737.3

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63598 AN: 151742 Hom.: 15575 Cov.: 31

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.420

GnomAD4 exome AF: 0.365 AC: 76 AN: 208 Hom.: 15 AF XY: 0.389 AC XY: 42 AN XY: 108

Gnomad4 AFR exome AF: 0.625

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.250

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.372

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.419 AC: 63666 AN: 151860 Hom.: 15602 Cov.: 31 AF XY: 0.409 AC XY: 30348 AN XY: 74248

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.416

Alfa AF: 0.396 Hom.: 2174

Bravo AF: 0.435

Asia WGS AF: 0.240 AC: 835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.53
DANN	Benign	0.55

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: rs2104533; hg19: chr9-95290456;