2-182201650-CAAAAA-CAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr2-182201650-C-CAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
• rs56413404
• NM_001363871.4:c.1004+37_1004+38insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

Variant summary

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

The NM_001363871.4(PDE1A):​c.1004+37_1004+38insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000177 in 1,131,586 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.543
• Publications: 0 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.1004+37_1004+38insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT		intron	N/A	NP_001350800.1	P54750-6
	PDE1A	NM_001258312.3		c.1064+37_1064+38insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT		intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.1052+37_1052+38insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT		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.1004+37_1004+38insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000386767.1	P54750-6
	PDE1A	ENST00000435564.6	TSL:1	c.1052+37_1052+38insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000410309.1	P54750-4
	PDE1A	ENST00000410103.2	TSL:1	c.1052+37_1052+38insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000387037.1	P54750-1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000177 AC: 2 AN: 1131586 Hom.: 0 Cov.: 25 AF XY: 0.00000354 AC XY: 2 AN XY: 564374

⚠️ 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: 24916

American (AMR) AF: 0.00 AC: 0 AN: 20796

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19088

East Asian (EAS) AF: 0.00 AC: 0 AN: 33686

South Asian (SAS) AF: 0.00 AC: 0 AN: 61072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36002

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4618

European-Non Finnish (NFE) AF: 0.00000226 AC: 2 AN: 883026

Other (OTH) AF: 0.00 AC: 0 AN: 48382

⚠️ 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 Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.54

Splicing

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

Other links and lift over

dbSNP: rs56413404; hg19: chr2-183066377;