5-114336545-C-T

Variant names:

• chr5-114336545-C-T
• rs10519381
• NM_001372233.1:c.-184-24400C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with or without variable movement or behavioral abnormalities

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KCNN2	NM_001372233.1	c.-184-24400C>T		intron_variant	Intron 4 of 12		NP_001359162.1
KCNN2	XM_011543389.2	c.-184-24400C>T		intron_variant	Intron 3 of 11		XP_011541691.1
KCNN2	XM_047417166.1	c.-1027-24400C>T		intron_variant	Intron 4 of 11		XP_047273122.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNN2	ENST00000512097.10	c.-184-24400C>T		intron_variant	Intron 4 of 12	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

African (AFR) AF: 0.218 AC: 9060 AN: 41486

American (AMR) AF: 0.329 AC: 5015 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 909 AN: 3466

East Asian (EAS) AF: 0.107 AC: 552 AN: 5164

South Asian (SAS) AF: 0.284 AC: 1368 AN: 4818

European-Finnish (FIN) AF: 0.310 AC: 3270 AN: 10550

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23709 AN: 67960

Other (OTH) AF: 0.331 AC: 696 AN: 2104

Alfa AF: 0.330 Hom.: 4768

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
PhyloP100		0.27

Splicing

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

Other links and lift over

dbSNP: rs10519381; hg19: chr5-113672242;