rs17799872

Variant names:

• chr2-24822088-G-A
• rs17799872
• NM_001322101.2:c.*2770G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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]

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]

ADCY3 Gene-Disease associations (from GenCC):

• body mass index quantitative trait locus 19

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPO	NM_001322101.2	MANE Select	c.*2770G>A		3_prime_UTR	Exon 8 of 8	NP_001309030.1
	ADCY3	NM_004036.5	MANE Select	c.3003+423C>T		intron	N/A	NP_004027.2
	CENPO	NR_136182.2		n.3622G>A		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPO	ENST00000380834.7	TSL:5 MANE Select	c.*2770G>A		3_prime_UTR	Exon 8 of 8	ENSP00000370214.2
	CENPO	ENST00000260662.2	TSL:1	c.*2770G>A		3_prime_UTR	Exon 8 of 8	ENSP00000260662.1
	ADCY3	ENST00000679454.1	MANE Select	c.3003+423C>T		intron	N/A	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

African (AFR) AF: 0.0606 AC: 72 AN: 1188

American (AMR) AF: 0.0495 AC: 145 AN: 2928

Ashkenazi Jewish (ASJ) AF: 0.0652 AC: 67 AN: 1028

East Asian (EAS) AF: 0.0268 AC: 59 AN: 2202

South Asian (SAS) AF: 0.0183 AC: 54 AN: 2948

European-Finnish (FIN) AF: 0.0627 AC: 89 AN: 1420

Middle Eastern (MID) AF: 0.0214 AC: 3 AN: 140

European-Non Finnish (NFE) AF: 0.0736 AC: 1678 AN: 22806

Other (OTH) AF: 0.0695 AC: 142 AN: 2044

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

African (AFR) AF: 0.0624 AC: 2594 AN: 41566

American (AMR) AF: 0.0606 AC: 928 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0700 AC: 243 AN: 3472

East Asian (EAS) AF: 0.0378 AC: 196 AN: 5184

South Asian (SAS) AF: 0.0205 AC: 99 AN: 4826

European-Finnish (FIN) AF: 0.0697 AC: 740 AN: 10618

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0788 AC: 5360 AN: 68026

Other (OTH) AF: 0.0867 AC: 183 AN: 2110

Alfa AF: 0.0757 Hom.: 794

Bravo AF: 0.0691

Asia WGS AF: 0.0320 AC: 111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.69
DANN	Benign	0.65
PhyloP100		-0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs17799872; hg19: chr2-25044957;