5-7545824-G-C

Variant names:

• chr5-7545824-G-C
• rs11747117
• NM_020546.3:c.570+24925G>C

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+24925G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 151,910 control chromosomes in the GnomAD database, including 23,337 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 0.53 (23337 hom., cov: 31)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.96
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.655 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.570+24925G>C		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.570+24925G>C		intron	N/A	ENSP00000342952.4
	ADCY2	ENST00000498598.1	TSL:5	n.269+24925G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80939 AN: 151792 Hom.: 23336 Cov.: 31

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.533 AC: 80954 AN: 151910 Hom.: 23337 Cov.: 31 AF XY: 0.531 AC XY: 39421 AN XY: 74260

African (AFR) AF: 0.349 AC: 14459 AN: 41382

American (AMR) AF: 0.442 AC: 6743 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2065 AN: 3466

East Asian (EAS) AF: 0.297 AC: 1523 AN: 5136

South Asian (SAS) AF: 0.492 AC: 2372 AN: 4826

European-Finnish (FIN) AF: 0.664 AC: 7006 AN: 10554

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.660 AC: 44856 AN: 67974

Other (OTH) AF: 0.522 AC: 1100 AN: 2106

Alfa AF: 0.500 Hom.: 1667

Bravo AF: 0.506

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.049
DANN	Benign	0.45
PhyloP100		-3.0
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: rs11747117; hg19: chr5-7545937;