chr19-590172-G-A
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_001194.4(HCN2):c.227G>A(p.Arg76His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 976,302 control chromosomes in the GnomAD database, including 118,627 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.39 ( 12023 hom., cov: 25)
Exomes 𝑓: 0.50 ( 106604 hom. )
Consequence
HCN2
NM_001194.4 missense
NM_001194.4 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 0.378
Genes affected
HCN2 (HGNC:4846): (hyperpolarization activated cyclic nucleotide gated potassium and sodium channel 2) The protein encoded by this gene is a hyperpolarization-activated cation channel involved in the generation of native pacemaker activity in the heart and in the brain. The encoded protein is activated by cAMP and can produce a fast, large current. Defects in this gene were noted as a possible cause of some forms of epilepsy. [provided by RefSeq, Jan 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0012045503).
BP6
Variant 19-590172-G-A is Benign according to our data. Variant chr19-590172-G-A is described in ClinVar as [Benign]. Clinvar id is 1291938.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HCN2 | NM_001194.4 | c.227G>A | p.Arg76His | missense_variant | 1/8 | ENST00000251287.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HCN2 | ENST00000251287.3 | c.227G>A | p.Arg76His | missense_variant | 1/8 | 1 | NM_001194.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.388 AC: 54896AN: 141624Hom.: 12026 Cov.: 25
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GnomAD3 exomes AF: 0.438 AC: 7AN: 16Hom.: 2 AF XY: 0.333 AC XY: 4AN XY: 12
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GnomAD4 exome AF: 0.501 AC: 418067AN: 834610Hom.: 106604 Cov.: 24 AF XY: 0.500 AC XY: 193093AN XY: 386144
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GnomAD4 genome AF: 0.387 AC: 54891AN: 141692Hom.: 12023 Cov.: 25 AF XY: 0.382 AC XY: 26336AN XY: 68882
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 04, 2020 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
P
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
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T
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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