chr5-7690088-A-G

Variant names:

• chr5-7690088-A-G
• rs7714830
• NM_020546.3:c.721-603A>G

Variant summary

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

The NM_020546.3(ADCY2):​c.721-603A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 152,244 control chromosomes in the GnomAD database, including 752 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 0.091 (752 hom., cov: 33)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY2	NM_020546.3	c.721-603A>G		intron_variant	Intron 4 of 24	ENST00000338316.9	NP_065433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY2	ENST00000338316.9	c.721-603A>G		intron_variant	Intron 4 of 24	1	NM_020546.3	ENSP00000342952.4
ADCY2	ENST00000515681.1	c.88-603A>G		intron_variant	Intron 2 of 3	4		ENSP00000425069.1
ADCY2	ENST00000513693.1	n.190-470A>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.0915 AC: 13916 AN: 152128 Hom.: 752 Cov.: 33

Gnomad AFR AF: 0.0319

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0781

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0898

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.0914 AC: 13913 AN: 152244 Hom.: 752 Cov.: 33 AF XY: 0.0905 AC XY: 6740 AN XY: 74436

African (AFR) AF: 0.0318 AC: 1323 AN: 41584

American (AMR) AF: 0.111 AC: 1698 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0781 AC: 271 AN: 3472

East Asian (EAS) AF: 0.200 AC: 1030 AN: 5158

South Asian (SAS) AF: 0.112 AC: 540 AN: 4828

European-Finnish (FIN) AF: 0.0898 AC: 952 AN: 10600

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7626 AN: 67998

Other (OTH) AF: 0.117 AC: 247 AN: 2114

Alfa AF: 0.107 Hom.: 1471

Bravo AF: 0.0904

Asia WGS AF: 0.170 AC: 588 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.83
DANN	Benign	0.65
PhyloP100		0.11
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: rs7714830; hg19: chr5-7690201;