rs1060499863
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001194.4(HCN2):c.246C>T(p.Cys82=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000119 in 837,266 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 0.0 ( 0 hom., cov: 29)
Exomes 𝑓: 0.0000012 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
HCN2
NM_001194.4 synonymous
NM_001194.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.108
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 Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
Variant 19-590191-C-T is Benign according to our data. Variant chr19-590191-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 402922.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.108 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HCN2 | NM_001194.4 | c.246C>T | p.Cys82= | synonymous_variant | 1/8 | ENST00000251287.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HCN2 | ENST00000251287.3 | c.246C>T | p.Cys82= | synonymous_variant | 1/8 | 1 | NM_001194.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 143926Hom.: 0 Cov.: 29 FAILED QC
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GnomAD4 exome AF: 0.00000119 AC: 1AN: 837266Hom.: 0 Cov.: 29 AF XY: 0.00000258 AC XY: 1AN XY: 387636
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GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 143926Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 69924
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Silent variant not near splice site - |
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