NM_020546.3:c.3123+2774G>A

Variant names:

• chr5-7823463-G-A
• rs9313204
• NM_020546.3:c.3123+2774G>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.3123+2774G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,952 control chromosomes in the GnomAD database, including 22,528 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 0.54 (22528 hom., cov: 32)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 1 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 (AMR) allele frequency at 95% confidence interval = 0.612 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.3123+2774G>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.3123+2774G>A		intron	N/A	ENSP00000342952.4	Q08462-1
	ADCY2	ENST00000915366.1		c.3126+2774G>A		intron	N/A	ENSP00000585425.1
	ADCY2	ENST00000915369.1		c.3021+2774G>A		intron	N/A	ENSP00000585428.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82073 AN: 151836 Hom.: 22521 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.540 AC: 82104 AN: 151952 Hom.: 22528 Cov.: 32 AF XY: 0.537 AC XY: 39919 AN XY: 74288

African (AFR) AF: 0.477 AC: 19746 AN: 41416

American (AMR) AF: 0.623 AC: 9512 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 2100 AN: 3472

East Asian (EAS) AF: 0.361 AC: 1863 AN: 5154

South Asian (SAS) AF: 0.472 AC: 2275 AN: 4820

European-Finnish (FIN) AF: 0.535 AC: 5657 AN: 10564

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.576 AC: 39116 AN: 67946

Other (OTH) AF: 0.575 AC: 1210 AN: 2106

Alfa AF: 0.547 Hom.: 12354

Bravo AF: 0.547

Asia WGS AF: 0.439 AC: 1527 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	0.14
DANN	Benign	0.64
PhyloP100		-1.5
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: rs9313204; hg19: chr5-7823576;