5-7545824-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020546.3(ADCY2):c.570+24925G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 151,910 control chromosomes in the GnomAD database, including 23,337 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 0.53 (23337 hom., cov: 31)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.96

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY2	NM_020546.3	c.570+24925G>C		intron_variant		ENST00000338316.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY2	ENST00000338316.9	c.570+24925G>C		intron_variant		1	NM_020546.3	P1
ADCY2	ENST00000498598.1	n.269+24925G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80939 AN: 151792 Hom.: 23336 Cov.: 31

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.533 AC: 80954 AN: 151910 Hom.: 23337 Cov.: 31 AF XY: 0.531 AC XY: 39421 AN XY: 74260

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.664

Gnomad4 NFE AF: 0.660

Gnomad4 OTH AF: 0.522

Alfa AF: 0.500 Hom.: 1667

Bravo AF: 0.506

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.049
Dann	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs11747117; hg19: chr5-7545937;