9-92494237-C-T

Variant names:

• chr9-92494237-C-T
• rs331380
• NM_001012267.3:c.564+114378C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001197296.2(ECM2):​c.1866-88G>A 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: ECM2 NM_001197296.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001197296.2. 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
	CENPP	NM_001012267.3	MANE Select	c.564+114378C>T		intron	N/A	NP_001012267.1
	ECM2	NM_001197296.2		c.1866-88G>A		intron	N/A	NP_001184225.1
	CENPP	NM_001286969.1		c.228+114378C>T		intron	N/A	NP_001273898.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPP	ENST00000375587.8	TSL:1 MANE Select	c.564+114378C>T		intron	N/A	ENSP00000364737.3
	ECM2	ENST00000444490.6	TSL:1	c.1866-88G>A		intron	N/A	ENSP00000393971.2

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

African (AFR) AF: 0.119 AC: 3398 AN: 28658

American (AMR) AF: 0.576 AC: 21654 AN: 37596

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 10323 AN: 22320

East Asian (EAS) AF: 0.757 AC: 27957 AN: 36918

South Asian (SAS) AF: 0.475 AC: 34021 AN: 71668

European-Finnish (FIN) AF: 0.549 AC: 19276 AN: 35118

Middle Eastern (MID) AF: 0.448 AC: 2327 AN: 5196

European-Non Finnish (NFE) AF: 0.507 AC: 463305 AN: 913760

Other (OTH) AF: 0.502 AC: 25899 AN: 51570

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

African (AFR) AF: 0.138 AC: 5734 AN: 41498

American (AMR) AF: 0.510 AC: 7795 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1641 AN: 3468

East Asian (EAS) AF: 0.798 AC: 4134 AN: 5182

South Asian (SAS) AF: 0.480 AC: 2313 AN: 4820

European-Finnish (FIN) AF: 0.539 AC: 5688 AN: 10560

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34225 AN: 67958

Other (OTH) AF: 0.437 AC: 922 AN: 2112

Alfa AF: 0.475 Hom.: 30539

Bravo AF: 0.400

Asia WGS AF: 0.600 AC: 2088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.2
DANN	Benign	0.66
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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