NM_001104631.2:c.809-2751G>A

Variant names:

• chr5-59041722-C-T
• rs1498606
• NM_001104631.2:c.809-2751G>A

Variant summary

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

The NM_001104631.2(PDE4D):​c.809-2751G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,204 control chromosomes in the GnomAD database, including 3,529 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 0.18 (3529 hom., cov: 32)
• Consequence: PDE4D NM_001104631.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570
• Publications: 10 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

ENSG00000247345 (HGNC:58182):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001104631.2. 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_001104631.2	MANE Select	c.809-2751G>A		intron	N/A	NP_001098101.1
	PDE4D	NM_001165899.2		c.626-2751G>A		intron	N/A	NP_001159371.1
	PDE4D	NM_001364599.1		c.626-2751G>A		intron	N/A	NP_001351528.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4D	ENST00000340635.11	TSL:1 MANE Select	c.809-2751G>A		intron	N/A	ENSP00000345502.6
	PDE4D	ENST00000502484.6	TSL:1	c.626-2751G>A		intron	N/A	ENSP00000423094.2
	PDE4D	ENST00000507116.6	TSL:1	c.617-2751G>A		intron	N/A	ENSP00000424852.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27929 AN: 152086 Hom.: 3526 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.184 AC: 27965 AN: 152204 Hom.: 3529 Cov.: 32 AF XY: 0.189 AC XY: 14064 AN XY: 74422

African (AFR) AF: 0.202 AC: 8381 AN: 41522

American (AMR) AF: 0.216 AC: 3301 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 393 AN: 3468

East Asian (EAS) AF: 0.709 AC: 3670 AN: 5176

South Asian (SAS) AF: 0.195 AC: 939 AN: 4824

European-Finnish (FIN) AF: 0.173 AC: 1837 AN: 10598

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8831 AN: 68010

Other (OTH) AF: 0.189 AC: 399 AN: 2112

Alfa AF: 0.155 Hom.: 7381

Bravo AF: 0.191

Asia WGS AF: 0.448 AC: 1553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.71
PhyloP100		0.057
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: rs1498606; hg19: chr5-58337549;