rs201253055
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000891.3(KCNJ2):c.1200G>A(p.Thr400=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00038 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000092 ( 0 hom. )
Consequence
KCNJ2
NM_000891.3 synonymous
NM_000891.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.402
Genes affected
KCNJ2 (HGNC:6263): (potassium inwardly rectifying channel subfamily J member 2) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, probably participates in establishing action potential waveform and excitability of neuronal and muscle tissues. Mutations in this gene have been associated with Andersen syndrome, which is characterized by periodic paralysis, cardiac arrhythmias, and dysmorphic features. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 17-70176239-G-A is Benign according to our data. Variant chr17-70176239-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 468463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.402 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000381 (58/152216) while in subpopulation AFR AF= 0.00108 (45/41538). AF 95% confidence interval is 0.000832. There are 0 homozygotes in gnomad4. There are 27 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 58 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNJ2 | NM_000891.3 | c.1200G>A | p.Thr400= | synonymous_variant | 2/2 | ENST00000243457.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNJ2 | ENST00000243457.4 | c.1200G>A | p.Thr400= | synonymous_variant | 2/2 | 1 | NM_000891.3 | P1 | |
KCNJ2 | ENST00000535240.1 | c.1200G>A | p.Thr400= | synonymous_variant | 2/2 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000381 AC: 58AN: 152098Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000155 AC: 39AN: 251082Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135726
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GnomAD4 exome AF: 0.0000923 AC: 135AN: 1461852Hom.: 0 Cov.: 32 AF XY: 0.000102 AC XY: 74AN XY: 727224
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GnomAD4 genome ? AF: 0.000381 AC: 58AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27AN XY: 74420
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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 provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 18, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | May 01, 2019 | - - |
Andersen Tawil syndrome;C1865018:Short QT syndrome type 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 27, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 09, 2016 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at