chr5-60174072-G-A

Variant names:

• chr5-60174072-G-A
• rs2910829
• ENST00000502484.6:c.42+11485C>T

Variant summary

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

The ENST00000502484.6(PDE4D):​c.42+11485C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,964 control chromosomes in the GnomAD database, including 20,142 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 0.51 (20142 hom., cov: 32)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786
• Publications: 31 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4D	NM_001165899.2	c.42+11485C>T		intron_variant	Intron 2 of 16		NP_001159371.1
PDE4D	NM_001364599.1	c.42+11485C>T		intron_variant	Intron 2 of 16		NP_001351528.1
PDE4D	NM_001349241.2	c.-62+11485C>T		intron_variant	Intron 2 of 17		NP_001336170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000502484.6	c.42+11485C>T		intron_variant	Intron 2 of 16	1		ENSP00000423094.2
PDE4D	ENST00000509355.5	n.288+11485C>T		intron_variant	Intron 2 of 2	1
PDE4D	ENST00000509368.6	n.42+11485C>T		intron_variant	Intron 2 of 4	1		ENSP00000423555.2

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77513 AN: 151846 Hom.: 20128 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.510 AC: 77550 AN: 151964 Hom.: 20142 Cov.: 32 AF XY: 0.508 AC XY: 37713 AN XY: 74278

African (AFR) AF: 0.488 AC: 20214 AN: 41426

American (AMR) AF: 0.540 AC: 8237 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1840 AN: 3472

East Asian (EAS) AF: 0.176 AC: 909 AN: 5166

South Asian (SAS) AF: 0.433 AC: 2089 AN: 4820

European-Finnish (FIN) AF: 0.580 AC: 6136 AN: 10572

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.534 AC: 36295 AN: 67950

Other (OTH) AF: 0.500 AC: 1055 AN: 2112

Alfa AF: 0.524 Hom.: 84985

Bravo AF: 0.512

Asia WGS AF: 0.288 AC: 1006 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.68
DANN	Benign	0.51
PhyloP100		-0.79
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: rs2910829; hg19: chr5-59469899;