rs9313203

Positions:

• chr5-7798960-G-A

Variant summary

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

The NM_020546.3(ADCY2):​c.2629-3258G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,036 control chromosomes in the GnomAD database, including 11,115 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 0.35 (11115 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY2	NM_020546.3	c.2629-3258G>A		intron_variant		ENST00000338316.9	NP_065433.2
ADCY2	XM_011513942.3	c.2491-3258G>A		intron_variant			XP_011512244.1
ADCY2	XM_047416645.1	c.2629-3258G>A		intron_variant			XP_047272601.1
ADCY2	XM_047416646.1	c.*32-3258G>A		intron_variant			XP_047272602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY2	ENST00000338316.9	c.2629-3258G>A		intron_variant		1	NM_020546.3	ENSP00000342952	P1
ADCY2	ENST00000489501.1	n.5342G>A		non_coding_transcript_exon_variant	1/5	2
ADCY2	ENST00000493243.5	c.*32-3258G>A		intron_variant, NMD_transcript_variant		5		ENSP00000426196
ADCY2	ENST00000382531.7	n.340-3258G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53040 AN: 151918 Hom.: 11120 Cov.: 31

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.0640

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.373

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.349 AC: 53038 AN: 152036 Hom.: 11115 Cov.: 31 AF XY: 0.347 AC XY: 25764 AN XY: 74302

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.498

Gnomad4 EAS AF: 0.0642

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.374

Alfa AF: 0.451 Hom.: 22104

Bravo AF: 0.325

Asia WGS AF: 0.232 AC: 808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.0
DANN	Benign	0.53

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: rs9313203; hg19: chr5-7799073;