rs758658597

Variant names:

• chr5-7396376-C-G
• rs758658597
• NM_020546.3:c.80C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-7396376-C-G
• chr5-7396376-C-A
• chr5-7396376-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020546.3(ADCY2):​c.80C>G​(p.Pro27Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,407,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ADCY2 NM_020546.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.372
• Publications: 1 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.101825565).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020546.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY2	NM_020546.3	MANE Select	c.80C>G	p.Pro27Arg	missense	Exon 1 of 25	NP_065433.2	Q08462-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY2	ENST00000338316.9	TSL:1 MANE Select	c.80C>G	p.Pro27Arg	missense	Exon 1 of 25	ENSP00000342952.4	Q08462-1
	ADCY2	ENST00000915366.1		c.80C>G	p.Pro27Arg	missense	Exon 1 of 25	ENSP00000585425.1
	ADCY2	ENST00000915369.1		c.80C>G	p.Pro27Arg	missense	Exon 1 of 24	ENSP00000585428.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000502 AC: 1 AN: 199104 AF XY: 0.00000902

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1407508 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 699734

African (AFR) AF: 0.00 AC: 0 AN: 29044

American (AMR) AF: 0.00 AC: 0 AN: 38940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24512

East Asian (EAS) AF: 0.00 AC: 0 AN: 33090

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 81742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5244

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1086036

Other (OTH) AF: 0.00 AC: 0 AN: 57698

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000831 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Benign	0.85
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.35	T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	-0.14	N
PhyloP100		-0.37
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.20
Sift	Uncertain	0.027	D
Sift4G	Benign	0.099	T
Polyphen		0.0	B
Vest4		0.060
MutPred		0.43		Gain of MoRF binding (P = 0.0176)
MVP		0.34
MPC		0.85
ClinPred		0.033	T
GERP RS		-0.63
PromoterAI		-0.0050	Neutral
Varity_R		0.051
gMVP		0.17
Mutation Taster		=98/2	polymorphism

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: rs758658597; hg19: chr5-7396489;