rs1187246548

Variant names:

• chr19-590187-C-A
• rs1187246548
• NM_001194.4:c.242C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-590187-C-A
• chr19-590187-C-G
• chr19-590187-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001194.4(HCN2):​c.242C>A​(p.Ser81*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HCN2 NM_001194.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353

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]

ENSG00000267036 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCN2	NM_001194.4	c.242C>A	p.Ser81*	stop_gained	Exon 1 of 8	ENST00000251287.3	NP_001185.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HCN2	ENST00000251287.3	c.242C>A	p.Ser81*	stop_gained	Exon 1 of 8	1	NM_001194.4	ENSP00000251287.1
ENSG00000267036	ENST00000589661.2	n.*243G>T		downstream_gene_variant		6

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 837390 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 387754

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	37
DANN	Benign	0.96
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.042	N
Vest4		0.23

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

Other links and lift over

dbSNP: rs1187246548; hg19: chr19-590187;