5-7396486-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020546.3(ADCY2):​c.190G>C​(p.Val64Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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)

Consequence

ADCY2
NM_020546.3 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.07
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19532731).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADCY2NM_020546.3 linkc.190G>C p.Val64Leu missense_variant 1/25 ENST00000338316.9 NP_065433.2 Q08462-1Q71UM8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ADCY2ENST00000338316.9 linkc.190G>C p.Val64Leu missense_variant 1/251 NM_020546.3 ENSP00000342952.4 Q08462-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 26, 2024The c.190G>C (p.V64L) alteration is located in exon 1 (coding exon 1) of the ADCY2 gene. This alteration results from a G to C substitution at nucleotide position 190, causing the valine (V) at amino acid position 64 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.25
BayesDel_addAF
Benign
-0.00048
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.20
T
Eigen
Benign
-0.38
Eigen_PC
Benign
-0.24
FATHMM_MKL
Benign
0.74
D
LIST_S2
Uncertain
0.89
D
M_CAP
Pathogenic
0.41
D
MetaRNN
Benign
0.20
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.70
N
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
-0.11
N
REVEL
Benign
0.25
Sift
Benign
0.35
T
Sift4G
Benign
0.80
T
Polyphen
0.0030
B
Vest4
0.20
MutPred
0.45
Loss of catalytic residue at V64 (P = 0.0322);
MVP
0.65
MPC
0.73
ClinPred
0.67
D
GERP RS
2.8
Varity_R
0.074
gMVP
0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-7396599; API