rs11742602

Variant names:

• chr5-7440494-G-T
• rs11742602
• NM_020546.3:c.408+25724G>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+25724G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,002 control chromosomes in the GnomAD database, including 14,797 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 0.44 (14797 hom., cov: 32)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.630
• Publications: 7 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.5 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY2	NM_020546.3	MANE Select	c.408+25724G>T		intron	N/A	NP_065433.2	Q08462-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY2	ENST00000338316.9	TSL:1 MANE Select	c.408+25724G>T		intron	N/A	ENSP00000342952.4	Q08462-1
	ADCY2	ENST00000915366.1		c.408+25724G>T		intron	N/A	ENSP00000585425.1
	ADCY2	ENST00000915369.1		c.408+25724G>T		intron	N/A	ENSP00000585428.1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66875 AN: 151884 Hom.: 14789 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.440 AC: 66915 AN: 152002 Hom.: 14797 Cov.: 32 AF XY: 0.440 AC XY: 32682 AN XY: 74280

African (AFR) AF: 0.435 AC: 18039 AN: 41438

American (AMR) AF: 0.482 AC: 7360 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1553 AN: 3468

East Asian (EAS) AF: 0.475 AC: 2455 AN: 5166

South Asian (SAS) AF: 0.517 AC: 2491 AN: 4820

European-Finnish (FIN) AF: 0.358 AC: 3782 AN: 10550

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29799 AN: 67972

Other (OTH) AF: 0.472 AC: 994 AN: 2108

Alfa AF: 0.435 Hom.: 8778

Bravo AF: 0.445

Asia WGS AF: 0.465 AC: 1617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.2
DANN	Benign	0.42
PhyloP100		0.63
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: rs11742602; hg19: chr5-7440607;