chr2-182201650-C-CAAAAAAAAAAA

Variant names:

• chr2-182201650-C-CAAAAAAAAAAA
• rs56413404
• NM_001363871.4:c.1004+27_1004+37dupTTTTTTTTTTT

Variant summary

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

The NM_001363871.4(PDE1A):​c.1004+27_1004+37dupTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.000022 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00019 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.543
• 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.1004+27_1004+37dupTTTTTTTTTTT		intron	N/A	NP_001350800.1	P54750-6
	PDE1A	NM_001258312.3		c.1064+27_1064+37dupTTTTTTTTTTT		intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.1052+27_1052+37dupTTTTTTTTTTT		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+38insTTTTTTTTTTT		intron	N/A	ENSP00000386767.1	P54750-6
	PDE1A	ENST00000435564.6	TSL:1	c.1052+37_1052+38insTTTTTTTTTTT		intron	N/A	ENSP00000410309.1	P54750-4
	PDE1A	ENST00000410103.2	TSL:1	c.1052+37_1052+38insTTTTTTTTTTT		intron	N/A	ENSP00000387037.1	P54750-1

Frequencies

GnomAD3 genomes AF: 0.0000219 AC: 3 AN: 136740 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000742

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: 0.0000310

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000188 AC: 213 AN: 1130902 Hom.: 4 Cov.: 25 AF XY: 0.000209 AC XY: 118 AN XY: 564034

⚠️ 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: 24912

American (AMR) AF: 0.00101 AC: 21 AN: 20738

Ashkenazi Jewish (ASJ) AF: 0.000262 AC: 5 AN: 19076

East Asian (EAS) AF: 0.000386 AC: 13 AN: 33650

South Asian (SAS) AF: 0.000525 AC: 32 AN: 60954

European-Finnish (FIN) AF: 0.000528 AC: 19 AN: 35968

Middle Eastern (MID) AF: 0.000433 AC: 2 AN: 4616

European-Non Finnish (NFE) AF: 0.000131 AC: 116 AN: 882636

Other (OTH) AF: 0.000103 AC: 5 AN: 48352

⚠️ 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 AF: 0.0000219 AC: 3 AN: 136740 Hom.: 0 Cov.: 0 AF XY: 0.0000154 AC XY: 1 AN XY: 65076

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

African (AFR) AF: 0.00 AC: 0 AN: 37724

American (AMR) AF: 0.0000742 AC: 1 AN: 13486

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3372

East Asian (EAS) AF: 0.00 AC: 0 AN: 4698

South Asian (SAS) AF: 0.00 AC: 0 AN: 4274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 298

European-Non Finnish (NFE) AF: 0.0000310 AC: 2 AN: 64538

Other (OTH) AF: 0.00 AC: 0 AN: 1876

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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;