chr5-7649747-C-T

Variant names:

• chr5-7649747-C-T
• rs4702484
• NM_020546.3:c.720+23431C>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.720+23431C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,220 control chromosomes in the GnomAD database, including 1,800 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 0.13 (1800 hom., cov: 33)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY2	NM_020546.3	c.720+23431C>T		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.720+23431C>T		intron_variant	Intron 4 of 24	1	NM_020546.3	ENSP00000342952.4
ADCY2	ENST00000515681.1	c.87+23431C>T		intron_variant	Intron 2 of 3	4		ENSP00000425069.1
ADCY2	ENST00000498598.1	n.420-8279C>T		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20212 AN: 152100 Hom.: 1798 Cov.: 33

Gnomad AFR AF: 0.0330

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.133 AC: 20217 AN: 152220 Hom.: 1800 Cov.: 33 AF XY: 0.138 AC XY: 10267 AN XY: 74404

African (AFR) AF: 0.0329 AC: 1366 AN: 41564

American (AMR) AF: 0.268 AC: 4103 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 411 AN: 3470

East Asian (EAS) AF: 0.196 AC: 1014 AN: 5168

South Asian (SAS) AF: 0.150 AC: 724 AN: 4814

European-Finnish (FIN) AF: 0.179 AC: 1902 AN: 10606

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10315 AN: 67994

Other (OTH) AF: 0.134 AC: 284 AN: 2114

Alfa AF: 0.144 Hom.: 6267

Bravo AF: 0.135

Asia WGS AF: 0.164 AC: 570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.71
PhyloP100		-0.023
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: rs4702484; hg19: chr5-7649860;