rs17725522

Variant names:

• chr5-59357247-T-C
• rs17725522
• NM_001104631.2:c.456-141279A>G

Variant summary

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

The NM_001104631.2(PDE4D):​c.456-141279A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.051 in 152,268 control chromosomes in the GnomAD database, including 293 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 0.051 (293 hom., cov: 32)
• Consequence: PDE4D NM_001104631.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.07
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4D	NM_001104631.2	c.456-141279A>G		intron_variant	Intron 1 of 14	ENST00000340635.11	NP_001098101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000340635.11	c.456-141279A>G		intron_variant	Intron 1 of 14	1	NM_001104631.2	ENSP00000345502.6

Frequencies

GnomAD3 genomes AF: 0.0511 AC: 7768 AN: 152150 Hom.: 293 Cov.: 32

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0443

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0430

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0684

Gnomad OTH AF: 0.0593

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

GnomAD4 genome AF: 0.0510 AC: 7764 AN: 152268 Hom.: 293 Cov.: 32 AF XY: 0.0510 AC XY: 3799 AN XY: 74454

African (AFR) AF: 0.0137 AC: 569 AN: 41560

American (AMR) AF: 0.0442 AC: 676 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 351 AN: 3470

East Asian (EAS) AF: 0.0127 AC: 66 AN: 5186

South Asian (SAS) AF: 0.156 AC: 751 AN: 4818

European-Finnish (FIN) AF: 0.0430 AC: 456 AN: 10608

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0683 AC: 4649 AN: 68018

Other (OTH) AF: 0.0587 AC: 124 AN: 2112

Alfa AF: 0.0526 Hom.: 38

Bravo AF: 0.0483

Asia WGS AF: 0.0770 AC: 267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.079
DANN	Benign	0.57
PhyloP100		-3.1
PromoterAI		0.028	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs17725522; hg19: chr5-58653073;