NM_020546.3:c.570+43003G>T

Variant names:

• chr5-7563902-G-T
• rs11134242
• NM_020546.3:c.570+43003G>T

Variant summary

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

The NM_020546.3(ADCY2):​c.570+43003G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,988 control chromosomes in the GnomAD database, including 8,997 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 0.33 (8997 hom., cov: 33)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.438
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.398 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.570+43003G>T		intron	N/A	NP_065433.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY2	ENST00000338316.9	TSL:1 MANE Select	c.570+43003G>T		intron	N/A	ENSP00000342952.4
	ADCY2	ENST00000915366.1		c.570+43003G>T		intron	N/A	ENSP00000585425.1
	ADCY2	ENST00000915369.1		c.570+43003G>T		intron	N/A	ENSP00000585428.1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49911 AN: 151870 Hom.: 8996 Cov.: 33

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.0171

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.329 AC: 49929 AN: 151988 Hom.: 8997 Cov.: 33 AF XY: 0.322 AC XY: 23932 AN XY: 74272

African (AFR) AF: 0.272 AC: 11262 AN: 41434

American (AMR) AF: 0.248 AC: 3791 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1530 AN: 3466

East Asian (EAS) AF: 0.0172 AC: 89 AN: 5178

South Asian (SAS) AF: 0.183 AC: 881 AN: 4822

European-Finnish (FIN) AF: 0.365 AC: 3846 AN: 10540

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27315 AN: 67972

Other (OTH) AF: 0.331 AC: 696 AN: 2104

Alfa AF: 0.271 Hom.: 1016

Bravo AF: 0.318

Asia WGS AF: 0.107 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.36
PhyloP100		0.44
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: rs11134242; hg19: chr5-7564015;