chr5-59769964-T-C

Variant names:

• chr5-59769964-T-C
• rs1504982
• NM_001104631.2:c.455+123204A>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.455+123204A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 151,944 control chromosomes in the GnomAD database, including 19,334 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 0.49 (19334 hom., cov: 31)
• Consequence: PDE4D NM_001104631.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 4 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

ENSG00000309959 (HGNC:):

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 = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4D	NM_001104631.2	c.455+123204A>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.455+123204A>G		intron_variant	Intron 1 of 14	1	NM_001104631.2	ENSP00000345502.6

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74451 AN: 151826 Hom.: 19309 Cov.: 31

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.490 AC: 74517 AN: 151944 Hom.: 19334 Cov.: 31 AF XY: 0.487 AC XY: 36178 AN XY: 74244

African (AFR) AF: 0.632 AC: 26169 AN: 41394

American (AMR) AF: 0.408 AC: 6226 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1499 AN: 3464

East Asian (EAS) AF: 0.142 AC: 735 AN: 5184

South Asian (SAS) AF: 0.393 AC: 1893 AN: 4818

European-Finnish (FIN) AF: 0.512 AC: 5400 AN: 10554

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31030 AN: 67946

Other (OTH) AF: 0.458 AC: 966 AN: 2108

Alfa AF: 0.440 Hom.: 4444

Bravo AF: 0.487

Asia WGS AF: 0.302 AC: 1051 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.51
PhyloP100		-1.2
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: rs1504982; hg19: chr5-59065790; COSMIC: COSV58948882; COSMIC: COSV58948882;