rs12520264

Positions:

• chr5-7645361-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020546.3(ADCY2):​c.720+19045G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,086 control chromosomes in the GnomAD database, including 4,417 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 0.21 (4417 hom., cov: 32)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY2	NM_020546.3	c.720+19045G>A		intron_variant		ENST00000338316.9	NP_065433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY2	ENST00000338316.9	c.720+19045G>A		intron_variant		1	NM_020546.3	ENSP00000342952	P1
ADCY2	ENST00000515681.1	c.87+19045G>A		intron_variant		4		ENSP00000425069
ADCY2	ENST00000498598.1	n.420-12665G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31802 AN: 151968 Hom.: 4420 Cov.: 32

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.209 AC: 31789 AN: 152086 Hom.: 4417 Cov.: 32 AF XY: 0.206 AC XY: 15340 AN XY: 74342

Gnomad4 AFR AF: 0.0617

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.206

Alfa AF: 0.282 Hom.: 8560

Bravo AF: 0.189

Asia WGS AF: 0.0690 AC: 239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs12520264; hg19: chr5-7645474;