5-7563902-G-T

Position:

• chr5-7563902-G-T

Variant summary

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

The NM_020546.3(ADCY2):​c.570+43003G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,988 control chromosomes in the GnomAD database, including 8,997 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 (8997 hom., cov: 33)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.438

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY2	NM_020546.3	c.570+43003G>T		intron_variant		ENST00000338316.9	NP_065433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY2	ENST00000338316.9	c.570+43003G>T		intron_variant		1	NM_020546.3	ENSP00000342952.4
ADCY2	ENST00000498598.1	n.269+43003G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49911 AN: 151870 Hom.: 8996 Cov.: 33

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.0171

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.329 AC: 49929 AN: 151988 Hom.: 8997 Cov.: 33 AF XY: 0.322 AC XY: 23932 AN XY: 74272

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.0172

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.331

Alfa AF: 0.270 Hom.: 979

Bravo AF: 0.318

Asia WGS AF: 0.107 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.36

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: rs11134242; hg19: chr5-7564015;