2-24820051-TG-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004036.5(ADCY3):c.3315del(p.Ile1106SerfsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ADCY3 NM_004036.5 frameshift
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 1.14

Genes affected

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: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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY3	NM_004036.5	c.3315del	p.Ile1106SerfsTer3	frameshift_variant	22/22	ENST00000679454.1
CENPO	NM_001322101.2	c.*737del		3_prime_UTR_variant	8/8	ENST00000380834.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY3	ENST00000679454.1	c.3315del	p.Ile1106SerfsTer3	frameshift_variant	22/22		NM_004036.5	P4
CENPO	ENST00000380834.7	c.*737del		3_prime_UTR_variant	8/8	5	NM_001322101.2	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 19 Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Feb 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1553329804; hg19: chr2-25042920;