15-84982316-G-C

Variant names:

• chr15-84982316-G-C
• rs943984676
• NM_002605.3:c.154G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002605.3(PDE8A):​c.154G>C​(p.Glu52Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDE8A NM_002605.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.749

Genes affected

PDE8A (HGNC:8793): (phosphodiesterase 8A) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE8 subfamily. This PDE hydrolyzes the second messenger, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011]

ACMG classification

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=0.18896678).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE8A	NM_002605.3	c.154G>C	p.Glu52Gln	missense_variant	Exon 1 of 22	ENST00000394553.6	NP_002596.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE8A	ENST00000394553.6	c.154G>C	p.Glu52Gln	missense_variant	Exon 1 of 22	1	NM_002605.3	ENSP00000378056.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Uncertain	0.97
DEOGEN2	Benign	0.14	T;T;.
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.74	T;.;T
M_CAP	Pathogenic	0.56	D
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.4	L;L;L
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.67	N;N;N
REVEL	Benign	0.072
Sift	Benign	0.064	T;T;D
Sift4G	Uncertain	0.042	D;D;D
Polyphen		0.24	B;B;P
Vest4		0.10
MutPred		0.32		Gain of MoRF binding (P = 0.0287);Gain of MoRF binding (P = 0.0287);Gain of MoRF binding (P = 0.0287);
MVP		0.43
MPC		0.23
ClinPred		0.11	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.24

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: rs943984676; hg19: chr15-85525547;