5-7519649-G-A

Variant names:

• chr5-7519649-G-A
• rs6867567
• NM_020546.3:c.409-1089G>A

Variant summary

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

The NM_020546.3(ADCY2):​c.409-1089G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 152,056 control chromosomes in the GnomAD database, including 42,402 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 0.74 (42402 hom., cov: 32)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.824 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.409-1089G>A		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.409-1089G>A		intron	N/A	ENSP00000342952.4
	ADCY2	ENST00000484965.5	TSL:3	n.143-1089G>A		intron	N/A
	ADCY2	ENST00000498598.1	TSL:5	n.108-1089G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112070 AN: 151936 Hom.: 42384 Cov.: 32

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.751

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

GnomAD4 genome AF: 0.737 AC: 112137 AN: 152056 Hom.: 42402 Cov.: 32 AF XY: 0.738 AC XY: 54880 AN XY: 74336

African (AFR) AF: 0.562 AC: 23261 AN: 41416

American (AMR) AF: 0.743 AC: 11348 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 2880 AN: 3470

East Asian (EAS) AF: 0.715 AC: 3697 AN: 5168

South Asian (SAS) AF: 0.723 AC: 3479 AN: 4810

European-Finnish (FIN) AF: 0.807 AC: 8546 AN: 10588

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.830 AC: 56416 AN: 68002

Other (OTH) AF: 0.749 AC: 1584 AN: 2116

Alfa AF: 0.793 Hom.: 82847

Bravo AF: 0.723

Asia WGS AF: 0.661 AC: 2300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.51
PhyloP100		-0.24
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: rs6867567; hg19: chr5-7519762;