rs2910830

Variant names:

• chr5-60171376-G-A
• rs2910830
• ENST00000502484.6:c.42+14181C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-60171376-G-A
• chr5-60171376-G-C
• chr5-60171376-G-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+14181C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 151,768 control chromosomes in the GnomAD database, including 27,842 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 0.60 (27842 hom., cov: 32)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 5 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 = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4D	NM_001165899.2	c.42+14181C>T		intron_variant	Intron 2 of 16		NP_001159371.1
PDE4D	NM_001364599.1	c.42+14181C>T		intron_variant	Intron 2 of 16		NP_001351528.1
PDE4D	NM_001349241.2	c.-62+14181C>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+14181C>T		intron_variant	Intron 2 of 16	1		ENSP00000423094.2
PDE4D	ENST00000509355.5	n.288+14181C>T		intron_variant	Intron 2 of 2	1
PDE4D	ENST00000509368.6	n.43-10559C>T		intron_variant	Intron 2 of 4	1		ENSP00000423555.2

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91076 AN: 151650 Hom.: 27828 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.600 AC: 91118 AN: 151768 Hom.: 27842 Cov.: 32 AF XY: 0.598 AC XY: 44333 AN XY: 74146

African (AFR) AF: 0.556 AC: 23008 AN: 41394

American (AMR) AF: 0.637 AC: 9699 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2198 AN: 3462

East Asian (EAS) AF: 0.239 AC: 1238 AN: 5170

South Asian (SAS) AF: 0.599 AC: 2888 AN: 4822

European-Finnish (FIN) AF: 0.654 AC: 6899 AN: 10546

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.635 AC: 43060 AN: 67834

Other (OTH) AF: 0.592 AC: 1241 AN: 2096

Alfa AF: 0.623 Hom.: 93703

Bravo AF: 0.597

Asia WGS AF: 0.411 AC: 1431 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.31
DANN	Benign	0.67
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: rs2910830; hg19: chr5-59467203;