Variant 19-590007-GGCC-G details in Genebe, Genetics Data Aggregator

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_83delGCC(p.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 0.00189 in 637,450 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000016 ( 0 hom., cov: 20)

Exomes 𝑓: 0.0024 ( 0 hom. )

Consequence

HCN2
NM_001194.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.460

Variant links:

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]

HCN2 links:

Genome browser will be placed here

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-GGCC-G is Benign according to our data. Variant chr19-590007-GGCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 3283623.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 1202 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCN2	NM_001194.4 linkuse as main transcript	c.81_83delGCC	p.Pro28del	disruptive_inframe_deletion	1/8	ENST00000251287.3	NP_001185.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HCN2	ENST00000251287.3 linkuse as main transcript	c.81_83delGCC	p.Pro28del	disruptive_inframe_deletion	1/8	1	NM_001194.4	ENSP00000251287.1		Q9UL51

Frequencies

GnomAD3 genomes

AF:

0.0000157

AC:

AN:

127068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000282

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000172

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00236

AC:

1202

AN:

510382

Hom.:

AF XY:

0.00242

AC XY:

577

AN XY:

238880

show subpopulations

Gnomad4 AFR exome

AF:

0.00207

Gnomad4 AMR exome

AF:

0.00469

Gnomad4 ASJ exome

AF:

0.00190

Gnomad4 EAS exome

AF:

0.00182

Gnomad4 SAS exome

AF:

0.00275

Gnomad4 FIN exome

AF:

0.00610

Gnomad4 NFE exome

AF:

0.00235

Gnomad4 OTH exome

AF:

0.00236

GnomAD4 genome

AF:

0.0000157

AC:

AN:

127068

Hom.:

Cov.:

AF XY:

0.0000162

AC XY:

AN XY:

61640

show subpopulations

Gnomad4 AFR

AF:

0.0000282

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000172

Gnomad4 OTH

AF:

0.00

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

May 07, 2024

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over