rs3215779

Positions:

• chr1-148960744-GA-G
• chr1-148960744-GA-GAA

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 8P and 2B. PVS1 BP6_Moderate

The NM_001395426.1(PDE4DIP):​c.927del​(p.Glu309AspfsTer23) variant causes a frameshift change. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 17)
  • Exomes 𝑓: 0.0058 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDE4DIP NM_001395426.1 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.95

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

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• BP6: Variant 1-148960744-GA-G is Benign according to our data. Variant chr1-148960744-GA-G is described in ClinVar as [Benign]. Clinvar id is 403294.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4DIP	NM_001395426.1	c.927del	p.Glu309AspfsTer23	frameshift_variant	9/47	ENST00000695795.1	NP_001382355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4DIP	ENST00000695795.1	c.927del	p.Glu309AspfsTer23	frameshift_variant	9/47		NM_001395426.1	ENSP00000512175

Frequencies

GnomAD3 genomes AF: 0.00 AC: 55 AN: 122224 Hom.: 0 Cov.: 17 FAILED QC

Gnomad AFR AF: 0.0000608

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000361

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.000952

Gnomad FIN AF: 0.000389

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000501

Gnomad OTH AF: 0.000650

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00583 AC: 2330 AN: 399700 Hom.: 0 Cov.: 4 AF XY: 0.00594 AC XY: 1239 AN XY: 208416

Gnomad4 AFR exome AF: 0.000252

Gnomad4 AMR exome AF: 0.0115

Gnomad4 ASJ exome AF: 0.00154

Gnomad4 EAS exome AF: 0.0120

Gnomad4 SAS exome AF: 0.0118

Gnomad4 FIN exome AF: 0.00434

Gnomad4 NFE exome AF: 0.00480

Gnomad4 OTH exome AF: 0.00430

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000441 AC: 54 AN: 122338 Hom.: 0 Cov.: 17 AF XY: 0.000534 AC XY: 31 AN XY: 58046

Gnomad4 AFR AF: 0.0000606

Gnomad4 AMR AF: 0.000360

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.000635

Gnomad4 FIN AF: 0.000389

Gnomad4 NFE AF: 0.000501

Gnomad4 OTH AF: 0.000643

Alfa AF: 0.0240 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC frequency -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3215779; hg19: chr1-144923731;