chr5-114463289-C-T

Position:

• chr5-114463289-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021614.4(KCNN2):​c.1779+99C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.044 in 895,398 control chromosomes in the GnomAD database, including 1,433 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.073 (681 hom., cov: 33)
  • Exomes 𝑓: 0.038 (752 hom.)
• Consequence: KCNN2 NM_021614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219

Genes affected

KCNN2 (HGNC:6291): (potassium calcium-activated channel subfamily N member 2) Action potentials in vertebrate neurons are followed by an afterhyperpolarization (AHP) that may persist for several seconds and may have profound consequences for the firing pattern of the neuron. Each component of the AHP is kinetically distinct and is mediated by different calcium-activated potassium channels. The protein encoded by this gene is activated before membrane hyperpolarization and is thought to regulate neuronal excitability by contributing to the slow component of synaptic AHP. This gene is a member of the KCNN family of potassium channel genes. The encoded protein is an integral membrane protein that forms a voltage-independent calcium-activated channel with three other calmodulin-binding subunits. Alternate splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]

KCNN2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNN2	NM_021614.4	c.1779+99C>T		intron_variant		ENST00000673685.1	NP_067627.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNN2	ENST00000673685.1	c.1779+99C>T		intron_variant			NM_021614.4	ENSP00000501239.1

Frequencies

GnomAD3 genomes AF: 0.0726 AC: 11045 AN: 152126 Hom.: 678 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0367

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.0397

Gnomad SAS AF: 0.0745

Gnomad FIN AF: 0.0555

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0334

Gnomad OTH AF: 0.0627

GnomAD4 exome AF: 0.0381 AC: 28345 AN: 743154 Hom.: 752 AF XY: 0.0386 AC XY: 14696 AN XY: 380870

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.0228

Gnomad4 ASJ exome AF: 0.0226

Gnomad4 EAS exome AF: 0.0251

Gnomad4 SAS exome AF: 0.0674

Gnomad4 FIN exome AF: 0.0543

Gnomad4 NFE exome AF: 0.0317

Gnomad4 OTH exome AF: 0.0450

GnomAD4 genome AF: 0.0727 AC: 11066 AN: 152244 Hom.: 681 Cov.: 33 AF XY: 0.0742 AC XY: 5525 AN XY: 74430

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.0366

Gnomad4 ASJ AF: 0.0184

Gnomad4 EAS AF: 0.0399

Gnomad4 SAS AF: 0.0739

Gnomad4 FIN AF: 0.0555

Gnomad4 NFE AF: 0.0334

Gnomad4 OTH AF: 0.0626

Alfa AF: 0.0503 Hom.: 83

Bravo AF: 0.0734

Asia WGS AF: 0.0630 AC: 219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.0
DANN	Benign	0.75

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: rs17136627; hg19: chr5-113798986;