rs10519381

Positions:

• chr5-114336545-C-T

Variant summary

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

The NM_001372233.1(KCNN2):​c.-184-24400C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,010 control chromosomes in the GnomAD database, including 7,028 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 0.30 (7028 hom., cov: 32)
• Consequence: KCNN2 NM_001372233.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNN2	NM_001372233.1	c.-184-24400C>T		intron_variant			NP_001359162.1
KCNN2	XM_011543389.2	c.-184-24400C>T		intron_variant			XP_011541691.1
KCNN2	XM_047417166.1	c.-1027-24400C>T		intron_variant			XP_047273122.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNN2	ENST00000512097.10	c.-184-24400C>T		intron_variant		5		ENSP00000427120.4

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45056 AN: 151892 Hom.: 7019 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.330

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.297 AC: 45105 AN: 152010 Hom.: 7028 Cov.: 32 AF XY: 0.294 AC XY: 21819 AN XY: 74312

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.331

Alfa AF: 0.329 Hom.: 4335

Bravo AF: 0.294

Asia WGS AF: 0.258 AC: 898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.9
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10519381; hg19: chr5-113672242;