chr2-24799722-C-T

Variant names:

• chr2-24799722-C-T
• rs143782986
• NM_001322101.2:c.94C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001322101.2(CENPO):​c.94C>T​(p.Arg32Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,614,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: CENPO NM_001322101.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.159
• Publications: 0 publications found

Genes affected

CENPO (HGNC:28152): (centromere protein O) This gene encodes a component of the interphase centromere complex. The encoded protein is localized to the centromere throughout the cell cycle and is required for bipolar spindle assembly, chromosome segregation and checkpoint signaling during mitosis. Alternatively spliced transcript variants encoding multiple protein isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.031950235).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001322101.2. 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
	CENPO	NM_001322101.2	MANE Select	c.94C>T	p.Arg32Cys	missense	Exon 3 of 8	NP_001309030.1	Q9BU64-1
	CENPO	NM_024322.4		c.94C>T	p.Arg32Cys	missense	Exon 3 of 8	NP_077298.1	Q9BU64-1
	CENPO	NM_001199803.3		c.76C>T	p.Arg26Cys	missense	Exon 2 of 7	NP_001186732.1	Q9BU64-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPO	ENST00000380834.7	TSL:5 MANE Select	c.94C>T	p.Arg32Cys	missense	Exon 3 of 8	ENSP00000370214.2	Q9BU64-1
	CENPO	ENST00000260662.2	TSL:1	c.94C>T	p.Arg32Cys	missense	Exon 3 of 8	ENSP00000260662.1	Q9BU64-1
	CENPO	ENST00000868050.1		c.94C>T	p.Arg32Cys	missense	Exon 3 of 8	ENSP00000538109.1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152118 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000597 AC: 15 AN: 251426 AF XY: 0.0000368

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000287 AC: 42 AN: 1461798 Hom.: 0 Cov.: 30 AF XY: 0.0000289 AC XY: 21 AN XY: 727198

African (AFR) AF: 0.000926 AC: 31 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111998

Other (OTH) AF: 0.0000331 AC: 2 AN: 60392

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152236 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74422

African (AFR) AF: 0.000554 AC: 23 AN: 41522

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.000264

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000741 AC: 9

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	10
DANN	Benign	0.88
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.66	N
PhyloP100		0.16
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.031
Sift	Benign	0.097	T
Sift4G	Benign	0.064	T
Polyphen		0.0060	B
Vest4		0.10
MVP		0.33
MPC		0.18
ClinPred		0.016	T
GERP RS		0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.060
gMVP		0.18
Mutation Taster		=90/10	polymorphism

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: rs143782986; hg19: chr2-25022591;