rs1588265

Variant names:

• chr5-60073967-A-C
• rs1588265
• ENST00000502484.6:c.43-85250T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-60073967-A-C
• chr5-60073967-A-G
• chr5-60073967-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001165899.2(PDE4D):​c.43-85250T>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PDE4D NM_001165899.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23
• Publications: 64 publications found

Genes affected

PDE4D (HGNC:8783): (phosphodiesterase 4D) This gene encodes one of four mammalian counterparts to the fruit fly 'dunce' gene. The encoded protein has 3',5'-cyclic-AMP phosphodiesterase activity and degrades cAMP, which acts as a signal transduction molecule in multiple cell types. This gene uses different promoters to generate multiple alternatively spliced transcript variants that encode functional proteins.[provided by RefSeq, Sep 2009]

PDE4D Gene-Disease associations (from GenCC):

• acrodysostosis 2 with or without hormone resistance

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• acrodysostosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• acrodysostosis with multiple hormone resistance

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• chromosome 5q12 deletion syndrome

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001165899.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4D	NM_001165899.2		c.43-85250T>G		intron	N/A	NP_001159371.1
	PDE4D	NM_001364599.1		c.43-85250T>G		intron	N/A	NP_001351528.1
	PDE4D	NM_001349241.2		c.-61-69621T>G		intron	N/A	NP_001336170.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4D	ENST00000502484.6	TSL:1	c.43-85250T>G		intron	N/A	ENSP00000423094.2
	PDE4D	ENST00000509355.5	TSL:1	n.289-85250T>G		intron	N/A
	PDE4D	ENST00000509368.6	TSL:1	n.*184+73781T>G		intron	N/A	ENSP00000423555.2

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.55
DANN	Benign	0.62
PhyloP100		-2.2

Splicing

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

Other links and lift over

dbSNP: rs1588265; hg19: chr5-59369794;