rs6555465

Variant names:

• chr5-7434504-A-G
• rs6555465
• NM_020546.3:c.408+19734A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-7434504-A-G
• chr5-7434504-A-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.408+19734A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 152,176 control chromosomes in the GnomAD database, including 50,963 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 0.81 (50963 hom., cov: 33)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936
• 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 (AFR) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY2	NM_020546.3	c.408+19734A>G		intron_variant	Intron 2 of 24	ENST00000338316.9	NP_065433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY2	ENST00000338316.9	c.408+19734A>G		intron_variant	Intron 2 of 24	1	NM_020546.3	ENSP00000342952.4
ADCY2	ENST00000484965.5	n.142+19734A>G		intron_variant	Intron 1 of 2	3
ADCY2	ENST00000498598.1	n.107+19734A>G		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123782 AN: 152058 Hom.: 50910 Cov.: 33

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.819

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

GnomAD4 genome AF: 0.814 AC: 123879 AN: 152176 Hom.: 50963 Cov.: 33 AF XY: 0.807 AC XY: 60053 AN XY: 74390

African (AFR) AF: 0.881 AC: 36582 AN: 41528

American (AMR) AF: 0.722 AC: 11035 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2933 AN: 3470

East Asian (EAS) AF: 0.491 AC: 2533 AN: 5162

South Asian (SAS) AF: 0.806 AC: 3882 AN: 4814

European-Finnish (FIN) AF: 0.758 AC: 8022 AN: 10588

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.827 AC: 56211 AN: 68002

Other (OTH) AF: 0.816 AC: 1726 AN: 2116

Alfa AF: 0.817 Hom.: 27575

Bravo AF: 0.807

Asia WGS AF: 0.634 AC: 2204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
DANN	Benign	0.55
PhyloP100		-0.94
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: rs6555465; hg19: chr5-7434617;