chr15-85109118-C-A

Variant names:

• chr15-85109118-C-A
• rs764756300
• NM_002605.3:c.1102C>A

Variant summary

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

The NM_002605.3(PDE8A):​c.1102C>A​(p.Arg368Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R368C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDE8A NM_002605.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002605.3. 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
	PDE8A	NM_002605.3	MANE Select	c.1102C>A	p.Arg368Ser	missense	Exon 12 of 22	NP_002596.1	O60658-1
	PDE8A	NM_173454.1		c.964C>A	p.Arg322Ser	missense	Exon 11 of 21	NP_775656.1	O60658-2
	PDE8A	NM_001243137.2		c.886C>A	p.Arg296Ser	missense	Exon 12 of 22	NP_001230066.1	O60658-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8A	ENST00000394553.6	TSL:1 MANE Select	c.1102C>A	p.Arg368Ser	missense	Exon 12 of 22	ENSP00000378056.1	O60658-1
	PDE8A	ENST00000310298.8	TSL:1	c.1102C>A	p.Arg368Ser	missense	Exon 13 of 23	ENSP00000311453.4	O60658-1
	PDE8A	ENST00000339708.9	TSL:1	c.964C>A	p.Arg322Ser	missense	Exon 11 of 21	ENSP00000340679.5	O60658-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	16
DANN	Benign	0.86
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.61
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.1
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.34
Sift	Benign	0.12	T
Sift4G	Benign	0.31	T
Polyphen		0.050	B
Vest4		0.70
MutPred		0.40		Gain of ubiquitination at K363 (P = 0.0211)
MVP		0.68
MPC		0.32
ClinPred		0.27	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.047
gMVP		0.53
Mutation Taster		=67/33	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: rs764756300; hg19: chr15-85652349; COSMIC: COSV59640446;