chr2-24831392-G-C

Variant names:

• chr2-24831392-G-C
• rs753529
• NM_004036.5:c.2055+270C>G

Variant summary

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

The NM_004036.5(ADCY3):​c.2055+270C>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADCY3 NM_004036.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 3 publications found

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]

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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004036.5. 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
	ADCY3	NM_004036.5	MANE Select	c.2055+270C>G		intron	N/A	NP_004027.2
	ADCY3	NM_001377128.1		c.2121+270C>G		intron	N/A	NP_001364057.1
	ADCY3	NM_001320613.2		c.2055+270C>G		intron	N/A	NP_001307542.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY3	ENST00000679454.1	MANE Select	c.2055+270C>G		intron	N/A	ENSP00000505261.1
	ADCY3	ENST00000405392.6	TSL:1	c.2055+270C>G		intron	N/A	ENSP00000384484.2
	ADCY3	ENST00000260600.9	TSL:1	c.2055+270C>G		intron	N/A	ENSP00000260600.5

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 5105

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.017
DANN	Benign	0.45
PhyloP100		-1.1

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: rs753529; hg19: chr2-25054261;