rs12189243

Variant names:

• chr5-7737361-T-C
• rs12189243
• NM_020546.3:c.1872-6307T>C

Variant summary

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

The NM_020546.3(ADCY2):​c.1872-6307T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,110 control chromosomes in the GnomAD database, including 9,964 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 (9964 hom., cov: 32)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98
• Publications: 2 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]

ENSG00000250761 (HGNC:40064):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY2	NM_020546.3	c.1872-6307T>C		intron_variant	Intron 14 of 24	ENST00000338316.9	NP_065433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY2	ENST00000338316.9	c.1872-6307T>C		intron_variant	Intron 14 of 24	1	NM_020546.3	ENSP00000342952.4
ENSG00000250761	ENST00000514105.2	n.162+8844A>G		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49873 AN: 151992 Hom.: 9964 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.0264

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.328 AC: 49858 AN: 152110 Hom.: 9964 Cov.: 32 AF XY: 0.325 AC XY: 24193 AN XY: 74350

African (AFR) AF: 0.140 AC: 5812 AN: 41524

American (AMR) AF: 0.257 AC: 3926 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1691 AN: 3462

East Asian (EAS) AF: 0.0259 AC: 134 AN: 5172

South Asian (SAS) AF: 0.303 AC: 1460 AN: 4822

European-Finnish (FIN) AF: 0.450 AC: 4758 AN: 10580

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30864 AN: 67968

Other (OTH) AF: 0.324 AC: 685 AN: 2114

Alfa AF: 0.412 Hom.: 57861

Bravo AF: 0.304

Asia WGS AF: 0.147 AC: 513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.62
DANN	Benign	0.73
PhyloP100		-2.0
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: rs12189243; hg19: chr5-7737474;