rs13174121

Variant names:

• chr5-7712370-G-C
• rs13174121
• NM_020546.3:c.1579-486G>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.1579-486G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,078 control chromosomes in the GnomAD database, including 16,526 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 0.45 (16526 hom., cov: 33)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• 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 (EAS) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY2	NM_020546.3	c.1579-486G>C		intron_variant	Intron 10 of 24	ENST00000338316.9	NP_065433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY2	ENST00000338316.9	c.1579-486G>C		intron_variant	Intron 10 of 24	1	NM_020546.3	ENSP00000342952.4
ENSG00000250761	ENST00000514105.2	n.163-4209C>G		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68354 AN: 151960 Hom.: 16502 Cov.: 33

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.450 AC: 68415 AN: 152078 Hom.: 16526 Cov.: 33 AF XY: 0.459 AC XY: 34094 AN XY: 74338

African (AFR) AF: 0.395 AC: 16374 AN: 41472

American (AMR) AF: 0.608 AC: 9289 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1228 AN: 3468

East Asian (EAS) AF: 0.954 AC: 4937 AN: 5176

South Asian (SAS) AF: 0.577 AC: 2780 AN: 4822

European-Finnish (FIN) AF: 0.422 AC: 4462 AN: 10572

Middle Eastern (MID) AF: 0.541 AC: 157 AN: 290

European-Non Finnish (NFE) AF: 0.409 AC: 27781 AN: 67980

Other (OTH) AF: 0.486 AC: 1025 AN: 2108

Alfa AF: 0.423 Hom.: 1740

Bravo AF: 0.463

Asia WGS AF: 0.725 AC: 2521 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	0.056
DANN	Benign	0.62
PhyloP100		-1.7
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: rs13174121; hg19: chr5-7712483;