rs7221086

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000891.3(KCNJ2):​c.660C>T​(p.Ser220=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,614,126 control chromosomes in the GnomAD database, including 1,983 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 1023 hom., cov: 32)
Exomes 𝑓: 0.0066 ( 960 hom. )

Consequence

KCNJ2
NM_000891.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 3.39
Variant links:
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 -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
Variant 17-70175699-C-T is Benign according to our data. Variant chr17-70175699-C-T is described in ClinVar as [Benign]. Clinvar id is 36434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-70175699-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=3.39 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KCNJ2NM_000891.3 linkuse as main transcriptc.660C>T p.Ser220= synonymous_variant 2/2 ENST00000243457.4 NP_000882.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KCNJ2ENST00000243457.4 linkuse as main transcriptc.660C>T p.Ser220= synonymous_variant 2/21 NM_000891.3 ENSP00000243457 P1
KCNJ2ENST00000535240.1 linkuse as main transcriptc.660C>T p.Ser220= synonymous_variant 2/21 ENSP00000441848 P1

Frequencies

GnomAD3 genomes
AF:
0.0627
AC:
9540
AN:
152116
Hom.:
1013
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.218
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0226
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00186
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.000853
Gnomad OTH
AF:
0.0459
GnomAD3 exomes
AF:
0.0170
AC:
4262
AN:
251412
Hom.:
437
AF XY:
0.0122
AC XY:
1656
AN XY:
135868
show subpopulations
Gnomad AFR exome
AF:
0.233
Gnomad AMR exome
AF:
0.00983
Gnomad ASJ exome
AF:
0.000794
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000359
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000598
Gnomad OTH exome
AF:
0.00749
GnomAD4 exome
AF:
0.00664
AC:
9714
AN:
1461892
Hom.:
960
Cov.:
32
AF XY:
0.00568
AC XY:
4131
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.233
Gnomad4 AMR exome
AF:
0.0120
Gnomad4 ASJ exome
AF:
0.000574
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000394
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000323
Gnomad4 OTH exome
AF:
0.0148
GnomAD4 genome
AF:
0.0629
AC:
9579
AN:
152234
Hom.:
1023
Cov.:
32
AF XY:
0.0612
AC XY:
4554
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.219
Gnomad4 AMR
AF:
0.0225
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00145
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000853
Gnomad4 OTH
AF:
0.0454
Alfa
AF:
0.0309
Hom.:
267
Bravo
AF:
0.0726
Asia WGS
AF:
0.0130
AC:
44
AN:
3478
EpiCase
AF:
0.000927
EpiControl
AF:
0.000830

ClinVar

Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Andersen Tawil syndrome;C1865018:Short QT syndrome type 3 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Atrial fibrillation, familial, 9 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Andersen Tawil syndrome Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitterclinical testingAmbry GeneticsJul 28, 2015This alteration is classified as 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. -
Short QT syndrome type 3 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Cardiac arrhythmia Benign:1
Benign, criteria provided, single submittercurationWomen's Health and Genetics/Laboratory Corporation of America, LabCorpAug 18, 2011- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
CADD
Benign
9.0
DANN
Benign
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7221086; hg19: chr17-68171840; API