chr2-24820123-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_004036.5(ADCY3):c.3253-9C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000717 in 1,534,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000051 ( 0 hom. )
Consequence
ADCY3
NM_004036.5 splice_polypyrimidine_tract, intron
NM_004036.5 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00005971
2
Clinical Significance
Conservation
PhyloP100: 0.204
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 2-24820123-G-A is Benign according to our data. Variant chr2-24820123-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3054987.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CENPO | NM_001322101.2 | c.*805G>A | 3_prime_UTR_variant | 8/8 | ENST00000380834.7 | ||
ADCY3 | NM_004036.5 | c.3253-9C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000679454.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CENPO | ENST00000380834.7 | c.*805G>A | 3_prime_UTR_variant | 8/8 | 5 | NM_001322101.2 | P1 | ||
ADCY3 | ENST00000679454.1 | c.3253-9C>T | splice_polypyrimidine_tract_variant, intron_variant | NM_004036.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152032Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000163 AC: 3AN: 184444Hom.: 0 AF XY: 0.0000102 AC XY: 1AN XY: 98006
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GnomAD4 exome AF: 0.00000506 AC: 7AN: 1382454Hom.: 0 Cov.: 32 AF XY: 0.00000588 AC XY: 4AN XY: 679760
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152150Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74376
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
ADCY3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 25, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at