rs17799872

Positions:

• chr2-24822088-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001322101.2(CENPO):​c.*2770G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0672 in 189,014 control chromosomes in the GnomAD database, including 485 homozygotes. 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: 𝑓 0.068 (388 hom., cov: 33)
  • Exomes 𝑓: 0.063 (97 hom.)
• Consequence: CENPO NM_001322101.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.739

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]

ADCY3 (HGNC:234): (adenylate cyclase 3) This gene encodes adenylyl cyclase 3 which is a membrane-associated enzyme and catalyzes the formation of the secondary messenger cyclic adenosine monophosphate (cAMP). This protein appears to be widely expressed in various human tissues and may be involved in a number of physiological and pathophysiological metabolic processes. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

CENPO (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.077 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPO	NM_001322101.2	c.*2770G>A		3_prime_UTR_variant	8/8	ENST00000380834.7	NP_001309030.1
ADCY3	NM_004036.5	c.3003+423C>T		intron_variant		ENST00000679454.1	NP_004027.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPO	ENST00000380834.7	c.*2770G>A		3_prime_UTR_variant	8/8	5	NM_001322101.2	ENSP00000370214.2
ADCY3	ENST00000679454.1	c.3003+423C>T		intron_variant			NM_004036.5	ENSP00000505261.1

Frequencies

GnomAD3 genomes AF: 0.0683 AC: 10395 AN: 152192 Hom.: 388 Cov.: 33

Gnomad AFR AF: 0.0624

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0609

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.0375

Gnomad SAS AF: 0.0207

Gnomad FIN AF: 0.0697

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0788

Gnomad OTH AF: 0.0876

GnomAD4 exome AF: 0.0629 AC: 2309 AN: 36704 Hom.: 97 Cov.: 0 AF XY: 0.0616 AC XY: 1157 AN XY: 18788

Gnomad4 AFR exome AF: 0.0606

Gnomad4 AMR exome AF: 0.0495

Gnomad4 ASJ exome AF: 0.0652

Gnomad4 EAS exome AF: 0.0268

Gnomad4 SAS exome AF: 0.0183

Gnomad4 FIN exome AF: 0.0627

Gnomad4 NFE exome AF: 0.0736

Gnomad4 OTH exome AF: 0.0695

GnomAD4 genome AF: 0.0683 AC: 10402 AN: 152310 Hom.: 388 Cov.: 33 AF XY: 0.0657 AC XY: 4891 AN XY: 74482

Gnomad4 AFR AF: 0.0624

Gnomad4 AMR AF: 0.0606

Gnomad4 ASJ AF: 0.0700

Gnomad4 EAS AF: 0.0378

Gnomad4 SAS AF: 0.0205

Gnomad4 FIN AF: 0.0697

Gnomad4 NFE AF: 0.0788

Gnomad4 OTH AF: 0.0867

Alfa AF: 0.0763 Hom.: 637

Bravo AF: 0.0691

Asia WGS AF: 0.0320 AC: 111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.69
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

LitVar

Other links and lift over

dbSNP: rs17799872; hg19: chr2-25044957;