rs1778111

Variant names:

• chr1-148968914-C-A
• rs1778111
• NM_001395426.1:c.2062C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-148968914-C-A
• chr1-148968914-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2 PP3_Moderate BP7

The NM_001395426.1(PDE4DIP):​c.2062C>A​(p.Arg688Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PDE4DIP NM_001395426.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 0 publications found

Genes affected

PDE4DIP (HGNC:15580): (phosphodiesterase 4D interacting protein) The protein encoded by this gene serves to anchor phosphodiesterase 4D to the Golgi/centrosome region of the cell. Defects in this gene may be a cause of myeloproliferative disorder (MBD) associated with eosinophilia. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: BayesDel_noAF computational evidence supports a deleterious effect, 0.44
• BP7: Synonymous conserved (PhyloP=1.03 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395426.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4DIP	NM_001395426.1	MANE Select	c.2062C>A	p.Arg688Arg	synonymous	Exon 17 of 47	NP_001382355.1	A0A8Q3SI83
	PDE4DIP	NM_001395297.1		c.2353C>A	p.Arg785Arg	synonymous	Exon 10 of 40	NP_001382226.1
	PDE4DIP	NM_001350520.2		c.2353C>A	p.Arg785Arg	synonymous	Exon 10 of 40	NP_001337449.1	A0A994J5E0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4DIP	ENST00000695795.1	MANE Select	c.2062C>A	p.Arg688Arg	synonymous	Exon 17 of 47	ENSP00000512175.1	A0A8Q3SI83
	PDE4DIP	ENST00000369356.8	TSL:1	c.1864C>A	p.Arg622Arg	synonymous	Exon 14 of 44	ENSP00000358363.4	Q5VU43-4
	PDE4DIP	ENST00000369354.7	TSL:1	c.1864C>A	p.Arg622Arg	synonymous	Exon 14 of 44	ENSP00000358360.3	Q5VU43-1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461244 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726998

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5684

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111560

Other (OTH) AF: 0.00 AC: 0 AN: 60364

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00109982), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Pathogenic	0.44
CADD	Benign	12
DANN	Benign	0.85
PhyloP100		1.0
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1778111; hg19: chr1-144915561;