7-31753453-G-C

Variant names:

• chr7-31753453-G-C
• NM_001191057.4:c.2061C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001191057.4(PDE1C):​c.2061C>G​(p.Tyr687*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PDE1C NM_001191057.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.360

Genes affected

PDE1C (HGNC:8776): (phosphodiesterase 1C) This gene encodes an enzyme that belongs to the 3'5'-cyclic nucleotide phosphodiesterase family. Members of this family catalyze hydrolysis of the cyclic nucleotides, cyclic adenosine monophosphate and cyclic guanosine monophosphate, to the corresponding nucleoside 5'-monophosphates. The enzyme encoded by this gene regulates proliferation and migration of vascular smooth muscle cells, and neointimal hyperplasia. This enzyme also plays a role in pathological vascular remodeling by regulating the stability of growth factor receptors, such as PDGF-receptor-beta. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE1C	NM_001191057.4	c.2061C>G	p.Tyr687*	stop_gained	Exon 18 of 18	ENST00000396191.6	NP_001177986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE1C	ENST00000396191.6	c.2061C>G	p.Tyr687*	stop_gained	Exon 18 of 18	2	NM_001191057.4	ENSP00000379494.1
PDE1C	ENST00000396193.5	c.2241C>G	p.Tyr747*	stop_gained	Exon 19 of 19	2		ENSP00000379496.1
PDE1C	ENST00000321453.12	c.2061C>G	p.Tyr687*	stop_gained	Exon 19 of 19	2		ENSP00000318105.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460342 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726468

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.54	D
BayesDel_noAF	Pathogenic	0.54
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Benign	0.016
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.66	D
Vest4		0.41
GERP RS		0.15

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-31793067;