NM_020546.3:c.408+30829C>A

Variant names:

• chr5-7445599-C-A
• rs13170330
• NM_020546.3:c.408+30829C>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.408+30829C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,154 control chromosomes in the GnomAD database, including 5,282 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 0.24 (5282 hom., cov: 33)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY2	NM_020546.3	MANE Select	c.408+30829C>A		intron	N/A	NP_065433.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY2	ENST00000338316.9	TSL:1 MANE Select	c.408+30829C>A		intron	N/A	ENSP00000342952.4
	ADCY2	ENST00000915366.1		c.408+30829C>A		intron	N/A	ENSP00000585425.1
	ADCY2	ENST00000915369.1		c.408+30829C>A		intron	N/A	ENSP00000585428.1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37186 AN: 152036 Hom.: 5287 Cov.: 33

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.244 AC: 37192 AN: 152154 Hom.: 5282 Cov.: 33 AF XY: 0.250 AC XY: 18587 AN XY: 74360

African (AFR) AF: 0.113 AC: 4692 AN: 41534

American (AMR) AF: 0.318 AC: 4862 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 887 AN: 3468

East Asian (EAS) AF: 0.475 AC: 2450 AN: 5156

South Asian (SAS) AF: 0.448 AC: 2153 AN: 4810

European-Finnish (FIN) AF: 0.230 AC: 2433 AN: 10588

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18849 AN: 68008

Other (OTH) AF: 0.264 AC: 558 AN: 2110

Alfa AF: 0.262 Hom.: 3112

Bravo AF: 0.240

Asia WGS AF: 0.416 AC: 1446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.62
PhyloP100		-1.3
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: rs13170330; hg19: chr5-7445712;