rs9313204

Positions:

• chr5-7823463-G-A
• chr5-7823463-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.3123+2774G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,952 control chromosomes in the GnomAD database, including 22,528 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 0.54 (22528 hom., cov: 32)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY2	NM_020546.3	c.3123+2774G>A		intron_variant		ENST00000338316.9	NP_065433.2
ADCY2	XM_011513942.3	c.2985+2774G>A		intron_variant			XP_011512244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY2	ENST00000338316.9	c.3123+2774G>A		intron_variant		1	NM_020546.3	ENSP00000342952	P1
ADCY2	ENST00000489501.1	n.9094+2774G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82073 AN: 151836 Hom.: 22521 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.540 AC: 82104 AN: 151952 Hom.: 22528 Cov.: 32 AF XY: 0.537 AC XY: 39919 AN XY: 74288

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.575

Alfa AF: 0.545 Hom.: 11027

Bravo AF: 0.547

Asia WGS AF: 0.439 AC: 1527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.64

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: rs9313204; hg19: chr5-7823576;