5-7662965-G-T

Variant names:

• chr5-7662965-G-T
• rs727432
• NM_020546.3:c.721-27726G>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.721-27726G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,068 control chromosomes in the GnomAD database, including 8,572 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 (8572 hom., cov: 33)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306
• Publications: 8 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]

ENSG00000305555 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.625 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.721-27726G>T		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.721-27726G>T		intron	N/A	ENSP00000342952.4
	ADCY2	ENST00000515681.1	TSL:4	c.88-27726G>T		intron	N/A	ENSP00000425069.1
	ENSG00000305555	ENST00000811684.1		n.-164C>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49597 AN: 151950 Hom.: 8566 Cov.: 33

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.326 AC: 49639 AN: 152068 Hom.: 8572 Cov.: 33 AF XY: 0.332 AC XY: 24666 AN XY: 74352

African (AFR) AF: 0.259 AC: 10732 AN: 41462

American (AMR) AF: 0.297 AC: 4543 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1117 AN: 3472

East Asian (EAS) AF: 0.643 AC: 3325 AN: 5168

South Asian (SAS) AF: 0.503 AC: 2426 AN: 4820

European-Finnish (FIN) AF: 0.368 AC: 3885 AN: 10570

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22601 AN: 67968

Other (OTH) AF: 0.338 AC: 716 AN: 2116

Alfa AF: 0.329 Hom.: 37859

Bravo AF: 0.317

Asia WGS AF: 0.538 AC: 1870 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	0.33
DANN	Benign	0.70
PhyloP100		-0.31
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: rs727432; hg19: chr5-7663078;