rs961585316

Variant names:

• chr19-590007-GGCCGCCGCCGCCGCC-G
• rs961585316
• NM_001194.4:c.69_83delGCCGCCGCCGCCGCC

Your query was ambiguous. Multiple possible variants found:

• chr19-590007-GGCCGCCGCCGCCGCC-G
• chr19-590007-GGCCGCCGCCGCCGCC-GGCC
• chr19-590007-GGCCGCCGCCGCCGCC-GGCCGCC
• chr19-590007-GGCCGCCGCCGCCGCC-GGCCGCCGCC
• chr19-590007-GGCCGCCGCCGCCGCC-GGCCGCCGCCGCC
• chr19-590007-GGCCGCCGCCGCCGCC-GGCCGCCGCCGCCGCCGCC
• chr19-590007-GGCCGCCGCCGCCGCC-GGCCGCCGCCGCCGCCGCCGCC
• chr19-590007-GGCCGCCGCCGCCGCC-GGCCGCCGCCGCCGCCGCCGCCGCC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_001194.4(HCN2):​c.69_83delGCCGCCGCCGCCGCC​(p.Pro24_Pro28del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000195 in 513,630 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: HCN2 NM_001194.4 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001194.4.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001194.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCN2	NM_001194.4	MANE Select	c.69_83delGCCGCCGCCGCCGCC	p.Pro24_Pro28del	disruptive_inframe_deletion	Exon 1 of 8	NP_001185.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCN2	ENST00000251287.3	TSL:1 MANE Select	c.69_83delGCCGCCGCCGCCGCC	p.Pro24_Pro28del	disruptive_inframe_deletion	Exon 1 of 8	ENSP00000251287.1	Q9UL51

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 0.00000195 AC: 1 AN: 513630 Hom.: 0 AF XY: 0.00000416 AC XY: 1 AN XY: 240408

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000103 AC: 1 AN: 9704

American (AMR) AF: 0.00 AC: 0 AN: 642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3182

East Asian (EAS) AF: 0.00 AC: 0 AN: 2216

South Asian (SAS) AF: 0.00 AC: 0 AN: 10234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 974

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 469898

Other (OTH) AF: 0.00 AC: 0 AN: 16616

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs961585316; hg19: chr19-590007;