rs331380

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr9-92494237-C-A
• chr9-92494237-C-G
• chr9-92494237-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001197296.2(ECM2):​c.1866-88G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,206,264 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000025 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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>A		intron	N/A	NP_001012267.1
	ECM2	NM_001197296.2		c.1866-88G>T		intron	N/A	NP_001184225.1
	CENPP	NM_001286969.1		c.228+114378C>A		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>A		intron	N/A	ENSP00000364737.3
	ECM2	ENST00000444490.6	TSL:1	c.1866-88G>T		intron	N/A	ENSP00000393971.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000249 AC: 3 AN: 1206264 Hom.: 0 AF XY: 0.00000166 AC XY: 1 AN XY: 603924

African (AFR) AF: 0.00 AC: 0 AN: 28690

American (AMR) AF: 0.00 AC: 0 AN: 37680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22374

East Asian (EAS) AF: 0.00 AC: 0 AN: 36980

South Asian (SAS) AF: 0.00 AC: 0 AN: 71876

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5208

European-Non Finnish (NFE) AF: 0.00000327 AC: 3 AN: 916496

Other (OTH) AF: 0.00 AC: 0 AN: 51760

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.8
DANN	Benign	0.63
PhyloP100		-0.27

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;