2-182201650-CAAAAA-CAAAAAAAA

Variant names:

• chr2-182201650-C-CAAA
• rs56413404
• NM_001363871.4:c.1004+35_1004+37dupTTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001363871.4(PDE1A):​c.1004+35_1004+37dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,108,824 control chromosomes in the GnomAD database, including 4,079 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2140 hom., cov: 0)
  • Exomes 𝑓: 0.18 (4079 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 2-182201650-C-CAAA is Benign according to our data. Variant chr2-182201650-C-CAAA is described in ClinVar as Benign. ClinVar VariationId is 1238438.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

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+35_1004+37dupTTT		intron	N/A	NP_001350800.1	P54750-6
	PDE1A	NM_001258312.3		c.1064+35_1064+37dupTTT		intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.1052+35_1052+37dupTTT		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+38insTTT		intron	N/A	ENSP00000386767.1	P54750-6
	PDE1A	ENST00000435564.6	TSL:1	c.1052+37_1052+38insTTT		intron	N/A	ENSP00000410309.1	P54750-4
	PDE1A	ENST00000410103.2	TSL:1	c.1052+37_1052+38insTTT		intron	N/A	ENSP00000387037.1	P54750-1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 21289 AN: 136562 Hom.: 2138 Cov.: 0

Gnomad AFR AF: 0.0777

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.178 AC: 197295 AN: 1108824 Hom.: 4079 Cov.: 25 AF XY: 0.176 AC XY: 97432 AN XY: 552740

African (AFR) AF: 0.0925 AC: 2250 AN: 24330

American (AMR) AF: 0.132 AC: 2675 AN: 20208

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 2098 AN: 18734

East Asian (EAS) AF: 0.264 AC: 8612 AN: 32674

South Asian (SAS) AF: 0.168 AC: 9947 AN: 59340

European-Finnish (FIN) AF: 0.209 AC: 7355 AN: 35266

Middle Eastern (MID) AF: 0.152 AC: 688 AN: 4528

European-Non Finnish (NFE) AF: 0.179 AC: 155468 AN: 866402

Other (OTH) AF: 0.173 AC: 8202 AN: 47342

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.156 AC: 21287 AN: 136560 Hom.: 2140 Cov.: 0 AF XY: 0.159 AC XY: 10316 AN XY: 65016

African (AFR) AF: 0.0778 AC: 2934 AN: 37736

American (AMR) AF: 0.119 AC: 1599 AN: 13476

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 437 AN: 3368

East Asian (EAS) AF: 0.303 AC: 1419 AN: 4678

South Asian (SAS) AF: 0.177 AC: 750 AN: 4244

European-Finnish (FIN) AF: 0.271 AC: 1513 AN: 5584

Middle Eastern (MID) AF: 0.175 AC: 48 AN: 274

European-Non Finnish (NFE) AF: 0.189 AC: 12194 AN: 64440

Other (OTH) AF: 0.147 AC: 276 AN: 1876

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.54
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV59541005;