5-7478801-G-A

Variant names:

• chr5-7478801-G-A
• rs252546
• NM_020546.3:c.409-41937G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020546.3(ADCY2):​c.409-41937G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 151,892 control chromosomes in the GnomAD database, including 34,080 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 0.67 (34080 hom., cov: 31)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 3 publications found

Genes affected

ADCY2 (HGNC:233): (adenylate cyclase 2) This gene encodes a member of the family of adenylate cyclases, which are membrane-associated enzymes that catalyze the formation of the secondary messenger cyclic adenosine monophosphate (cAMP). This enzyme is insensitive to Ca(2+)/calmodulin, and is stimulated by the G protein beta and gamma subunit complex. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020546.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY2	NM_020546.3	MANE Select	c.409-41937G>A		intron	N/A	NP_065433.2	Q08462-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY2	ENST00000338316.9	TSL:1 MANE Select	c.409-41937G>A		intron	N/A	ENSP00000342952.4	Q08462-1
	ADCY2	ENST00000915366.1		c.409-41937G>A		intron	N/A	ENSP00000585425.1
	ADCY2	ENST00000915369.1		c.409-41937G>A		intron	N/A	ENSP00000585428.1

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101146 AN: 151772 Hom.: 34050 Cov.: 31

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.666 AC: 101222 AN: 151892 Hom.: 34080 Cov.: 31 AF XY: 0.661 AC XY: 49068 AN XY: 74188

African (AFR) AF: 0.751 AC: 31126 AN: 41468

American (AMR) AF: 0.645 AC: 9830 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2367 AN: 3470

East Asian (EAS) AF: 0.574 AC: 2948 AN: 5136

South Asian (SAS) AF: 0.444 AC: 2140 AN: 4818

European-Finnish (FIN) AF: 0.633 AC: 6673 AN: 10544

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43897 AN: 67902

Other (OTH) AF: 0.659 AC: 1394 AN: 2114

Alfa AF: 0.653 Hom.: 100202

Bravo AF: 0.675

Asia WGS AF: 0.540 AC: 1876 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.040
DANN	Benign	0.45
PhyloP100		-1.7
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: rs252546; hg19: chr5-7478914;