2-24799748-C-A

Variant names:

• chr2-24799748-C-A
• rs750497004
• NM_001322101.2:c.120C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001322101.2(CENPO):​c.120C>A​(p.Ser40Arg) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CENPO NM_001322101.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.739
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03306696).
• BP6: Variant 2-24799748-C-A is Benign according to our data. Variant chr2-24799748-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3490403.Status of the report is criteria_provided_single_submitter, 1 stars.

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.120C>A	p.Ser40Arg	missense	Exon 3 of 8	NP_001309030.1	Q9BU64-1
	CENPO	NM_024322.4		c.120C>A	p.Ser40Arg	missense	Exon 3 of 8	NP_077298.1	Q9BU64-1
	CENPO	NM_001199803.3		c.102C>A	p.Ser34Arg	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.120C>A	p.Ser40Arg	missense	Exon 3 of 8	ENSP00000370214.2	Q9BU64-1
	CENPO	ENST00000260662.2	TSL:1	c.120C>A	p.Ser40Arg	missense	Exon 3 of 8	ENSP00000260662.1	Q9BU64-1
	CENPO	ENST00000868050.1		c.120C>A	p.Ser40Arg	missense	Exon 3 of 8	ENSP00000538109.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.087
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.017
DANN	Benign	0.20
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0038	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.74
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.039
Sift	Benign	0.59	T
Sift4G	Benign	0.60	T
Polyphen		0.0010	B
Vest4		0.074
MutPred		0.26		Gain of MoRF binding (P = 0.0079)
MVP		0.10
MPC		0.15
ClinPred		0.016	T
GERP RS		-6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.044
gMVP		0.12
Mutation Taster		=99/1	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: rs750497004; hg19: chr2-25022617;