chr19-590007-G-GGCC
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PM4_SupportingBP6_ModerateBS2
The NM_001194.4(HCN2):c.81_83dup(p.Pro27dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00088 ( 1 hom., cov: 20)
Exomes 𝑓: 0.000064 ( 0 hom. )
Consequence
HCN2
NM_001194.4 inframe_insertion
NM_001194.4 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.460
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.
PM4
?
Nonframeshift variant in NON repetitive region in NM_001194.4. Strenght limited to Supporting due to length of the change: 1aa.
BP6
?
Variant 19-590007-G-GGCC is Benign according to our data. Variant chr19-590007-G-GGCC is described in ClinVar as [Likely_benign]. Clinvar id is 2357092.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 110 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HCN2 | NM_001194.4 | c.81_83dup | p.Pro27dup | inframe_insertion | 1/8 | ENST00000251287.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HCN2 | ENST00000251287.3 | c.81_83dup | p.Pro27dup | inframe_insertion | 1/8 | 1 | NM_001194.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000866 AC: 110AN: 127064Hom.: 1 Cov.: 20
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GnomAD4 exome AF: 0.0000643 AC: 33AN: 513590Hom.: 0 Cov.: 4 AF XY: 0.0000499 AC XY: 12AN XY: 240392
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GnomAD4 genome ? AF: 0.000882 AC: 112AN: 127052Hom.: 1 Cov.: 20 AF XY: 0.000973 AC XY: 60AN XY: 61642
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 19, 2022 | 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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Find out detailed SpliceAI scores and Pangolin per-transcript scores at