chr2-24793939-T-C

Variant names:

• chr2-24793939-T-C
• NM_001322101.2:c.20T>C

Variant summary

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

The NM_001322101.2(CENPO):​c.20T>C​(p.Leu7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CENPO NM_001322101.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.22
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06749353).

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.20T>C	p.Leu7Ser	missense	Exon 2 of 8	NP_001309030.1	Q9BU64-1
	CENPO	NM_024322.4		c.20T>C	p.Leu7Ser	missense	Exon 2 of 8	NP_077298.1	Q9BU64-1
	CENPO	NM_001199803.3		c.28+438T>C		intron	N/A	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.20T>C	p.Leu7Ser	missense	Exon 2 of 8	ENSP00000370214.2	Q9BU64-1
	CENPO	ENST00000260662.2	TSL:1	c.20T>C	p.Leu7Ser	missense	Exon 2 of 8	ENSP00000260662.1	Q9BU64-1
	CENPO	ENST00000868050.1		c.20T>C	p.Leu7Ser	missense	Exon 2 of 8	ENSP00000538109.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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	0.066
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.60
DANN	Benign	0.69
DEOGEN2	Benign	0.0093	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0061	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		-1.2
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.018
Sift	Benign	0.093	T
Sift4G	Benign	0.19	T
Polyphen		0.0040	B
Vest4		0.10
MutPred		0.14		Gain of phosphorylation at L7 (P = 0.0103)
MVP		0.35
MPC		0.19
ClinPred		0.068	T
GERP RS		-0.47
PromoterAI		-0.092	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.036
gMVP		0.26
Mutation Taster		=97/3	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

hg19: chr2-25016808;