rs534955473

Variant names:

• chr9-92509917-C-G
• NM_001393.4:c.1288G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-92509917-C-G
• chr9-92509917-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001393.4(ECM2):​c.1288G>C​(p.Asp430His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ECM2 NM_001393.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16736874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECM2	NM_001393.4	c.1288G>C	p.Asp430His	missense_variant	Exon 6 of 10	ENST00000344604.10	NP_001384.1
CENPP	NM_001012267.3	c.565-101397C>G		intron_variant	Intron 5 of 7	ENST00000375587.8	NP_001012267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECM2	ENST00000344604.10	c.1288G>C	p.Asp430His	missense_variant	Exon 6 of 10	1	NM_001393.4	ENSP00000344758.5
ECM2	ENST00000444490.6	c.1222G>C	p.Asp408His	missense_variant	Exon 6 of 10	1		ENSP00000393971.2
CENPP	ENST00000375587.8	c.565-101397C>G		intron_variant	Intron 5 of 7	1	NM_001012267.3	ENSP00000364737.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450420 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 721458

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Benign	0.92
DEOGEN2	Benign	0.048	.;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.60	.;N
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.043
Sift	Benign	0.087	T;T
Sift4G	Uncertain	0.011	D;D
Polyphen		0.55	P;B
Vest4		0.30
MutPred		0.31		.;Loss of loop (P = 0.1242);
MVP		0.84
MPC		0.084
ClinPred		0.52	D
GERP RS		2.5
Varity_R		0.14
gMVP		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-95272199;