rs200218082
Positions:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_006258.4(PRKG1):c.1002-9G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000199 in 1,610,520 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00019 ( 1 hom. )
Consequence
PRKG1
NM_006258.4 splice_polypyrimidine_tract, intron
NM_006258.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0006690
2
Clinical Significance
Conservation
PhyloP100: 0.0310
Genes affected
PRKG1 (HGNC:9414): (protein kinase cGMP-dependent 1) Mammals have three different isoforms of cyclic GMP-dependent protein kinase (Ialpha, Ibeta, and II). These PRKG isoforms act as key mediators of the nitric oxide/cGMP signaling pathway and are important components of many signal transduction processes in diverse cell types. This PRKG1 gene on human chromosome 10 encodes the soluble Ialpha and Ibeta isoforms of PRKG by alternative transcript splicing. A separate gene on human chromosome 4, PRKG2, encodes the membrane-bound PRKG isoform II. The PRKG1 proteins play a central role in regulating cardiovascular and neuronal functions in addition to relaxing smooth muscle tone, preventing platelet aggregation, and modulating cell growth. This gene is most strongly expressed in all types of smooth muscle, platelets, cerebellar Purkinje cells, hippocampal neurons, and the lateral amygdala. Isoforms Ialpha and Ibeta have identical cGMP-binding and catalytic domains but differ in their leucine/isoleucine zipper and autoinhibitory sequences and therefore differ in their dimerization substrates and kinase enzyme activity. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 10-52161880-G-A is Benign according to our data. Variant chr10-52161880-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 414275.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-52161880-G-A is described in Lovd as [Likely_benign].
BS2
?
High AC in GnomAd4 at 37 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKG1 | NM_006258.4 | c.1002-9G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000373980.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKG1 | ENST00000373980.11 | c.1002-9G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_006258.4 |
Frequencies
GnomAD3 genomes ? AF: 0.000244 AC: 37AN: 151780Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000217 AC: 54AN: 249022Hom.: 0 AF XY: 0.000186 AC XY: 25AN XY: 134608
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GnomAD4 exome AF: 0.000194 AC: 283AN: 1458622Hom.: 1 Cov.: 31 AF XY: 0.000178 AC XY: 129AN XY: 725580
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GnomAD4 genome ? AF: 0.000244 AC: 37AN: 151898Hom.: 0 Cov.: 33 AF XY: 0.000270 AC XY: 20AN XY: 74196
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 08, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 10, 2023 | - - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Aortic aneurysm, familial thoracic 8 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 10, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at