PDE4A p.Thr247Thr

Variant names:

• chr19-10450896-G-G
• NM_001111307.2:c.

Your query was ambiguous. Multiple possible variants found:

• chr19-10450897--
• chr19-10450899-C-T
• chr19-10450899-C-A
• chr19-10450899-C-G

Variant summary

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

The NM_001111307.2(PDE4A):​c. variant causes a exon region change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDE4A NM_001111307.2 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.11
• Publications: 0 publications found

Genes affected

PDE4A (HGNC:8780): (phosphodiesterase 4A) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 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 described 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_001111307.2. 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
	PDE4A	NM_001111307.2	MANE Select	c.		exon_region	Exon 8 of 15	NP_001104777.1	P27815-1
	PDE4A	NM_001243121.2		c.		exon_region	Exon 10 of 17	NP_001230050.1	P27815-7
	PDE4A	NM_001111308.1		c.		exon_region	Exon 8 of 15	NP_001104778.1	P27815-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4A	ENST00000380702.7	TSL:1 MANE Select	c.		splice_donor intron	N/A	ENSP00000370078.3	P27815-1
	PDE4A	ENST00000592685.5	TSL:1	c.		splice_donor intron	N/A	ENSP00000468507.1	P27815-7
	PDE4A	ENST00000293683.9	TSL:1	c.		splice_donor intron	N/A	ENSP00000293683.4	P27815-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-10561572;