NM_001363871.4:c.1516+17597_1516+17598dupTT

Variant names:

• chr2-182168293-G-GAA
• rs78156757
• NM_001363871.4:c.1516+17597_1516+17598dupTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001363871.4(PDE1A):​c.1516+17597_1516+17598dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 25)
  • Exomes 𝑓: 0.00038 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.659
• Publications: 1 publications found

Genes affected

PDE1A (HGNC:8774): (phosphodiesterase 1A) Cyclic nucleotide phosphodiesterases (PDEs) play a role in signal transduction by regulating intracellular cyclic nucleotide concentrations through hydrolysis of cAMP and/or cGMP to their respective nucleoside 5-prime monophosphates. Members of the PDE1 family, such as PDE1A, are Ca(2+)/calmodulin (see CALM1; MIM 114180)-dependent PDEs (CaM-PDEs) that are activated by calmodulin in the presence of Ca(2+) (Michibata et al., 2001 [PubMed 11342109]; Fidock et al., 2002 [PubMed 11747989]).[supplied by OMIM, Oct 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363871.4. 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
	PDE1A	NM_001363871.4	MANE Select	c.1516+17597_1516+17598dupTT		intron	N/A	NP_001350800.1	P54750-6
	PDE1A	NM_001258312.3		c.1576+17597_1576+17598dupTT		intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.1564+17597_1564+17598dupTT		intron	N/A	NP_001382187.1	P54750-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1A	ENST00000409365.6	TSL:5 MANE Select	c.1516+17598_1516+17599insTT		intron	N/A	ENSP00000386767.1	P54750-6
	PDE1A	ENST00000435564.6	TSL:1	c.1564+17598_1564+17599insTT		intron	N/A	ENSP00000410309.1	P54750-4
	PDE1A	ENST00000410103.2	TSL:1	c.1565-4_1565-3insTT		splice_region intron	N/A	ENSP00000387037.1	P54750-1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 135890 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000826 AC: 95 AN: 114962 AF XY: 0.000878

Gnomad AFR exome AF: 0.000698

Gnomad AMR exome AF: 0.000997

Gnomad ASJ exome AF: 0.00186

Gnomad EAS exome AF: 0.000860

Gnomad FIN exome AF: 0.000593

Gnomad NFE exome AF: 0.000713

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000381 AC: 447 AN: 1172506 Hom.: 0 Cov.: 0 AF XY: 0.000448 AC XY: 261 AN XY: 583212

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

African (AFR) AF: 0.000815 AC: 21 AN: 25758

American (AMR) AF: 0.000499 AC: 14 AN: 28046

Ashkenazi Jewish (ASJ) AF: 0.000743 AC: 15 AN: 20200

East Asian (EAS) AF: 0.000425 AC: 14 AN: 32938

South Asian (SAS) AF: 0.00153 AC: 98 AN: 63956

European-Finnish (FIN) AF: 0.000548 AC: 23 AN: 41970

Middle Eastern (MID) AF: 0.000437 AC: 2 AN: 4578

European-Non Finnish (NFE) AF: 0.000264 AC: 239 AN: 906908

Other (OTH) AF: 0.000436 AC: 21 AN: 48152

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 135890 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 65378

African (AFR) AF: 0.00 AC: 0 AN: 37126

American (AMR) AF: 0.00 AC: 0 AN: 13824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3210

East Asian (EAS) AF: 0.00 AC: 0 AN: 4850

South Asian (SAS) AF: 0.00 AC: 0 AN: 4396

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 62144

Other (OTH) AF: 0.00 AC: 0 AN: 1832

Alfa AF: 0.00193 Hom.: 98

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.66
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs78156757; hg19: chr2-183033020;