rs10059859

Variant names:

• chr5-59935480-C-T
• rs10059859
• ENST00000502484.6:c.272+53008G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000502484.6(PDE4D):​c.272+53008G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,042 control chromosomes in the GnomAD database, including 11,399 homozygotes. 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: 𝑓 0.27 (11399 hom., cov: 32)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4D	NM_001165899.2	c.272+53008G>A		intron_variant	Intron 3 of 16		NP_001159371.1
PDE4D	NM_001364599.1	c.272+53008G>A		intron_variant	Intron 3 of 16		NP_001351528.1
PDE4D	NM_001349241.2	c.242+53008G>A		intron_variant	Intron 4 of 17		NP_001336170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000502484.6	c.272+53008G>A		intron_variant	Intron 3 of 16	1		ENSP00000423094.2
PDE4D	ENST00000512069.6	n.217+53008G>A		intron_variant	Intron 1 of 2	2
PDE4D	ENST00000514231.1	n.145+53008G>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40603 AN: 151926 Hom.: 11348 Cov.: 32

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.0893

Gnomad SAS AF: 0.0915

Gnomad FIN AF: 0.0299

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.0934

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.268 AC: 40704 AN: 152042 Hom.: 11399 Cov.: 32 AF XY: 0.258 AC XY: 19193 AN XY: 74330

African (AFR) AF: 0.712 AC: 29499 AN: 41426

American (AMR) AF: 0.143 AC: 2192 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 764 AN: 3470

East Asian (EAS) AF: 0.0893 AC: 461 AN: 5162

South Asian (SAS) AF: 0.0905 AC: 437 AN: 4828

European-Finnish (FIN) AF: 0.0299 AC: 317 AN: 10600

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.0933 AC: 6344 AN: 67966

Other (OTH) AF: 0.250 AC: 529 AN: 2112

Alfa AF: 0.158 Hom.: 8004

Bravo AF: 0.298

Asia WGS AF: 0.135 AC: 471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.035
DANN	Benign	0.60
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10059859; hg19: chr5-59231307;