5-114343507-T-C

Variant names:

• chr5-114343507-T-C
• rs36936
• NM_001372233.1:c.-184-17438T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001372233.1(KCNN2):​c.-184-17438T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 152,056 control chromosomes in the GnomAD database, including 48,551 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 0.80 (48551 hom., cov: 31)
• Consequence: KCNN2 NM_001372233.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNN2	NM_001372233.1	c.-184-17438T>C		intron_variant	Intron 4 of 12		NP_001359162.1
KCNN2	XM_011543389.2	c.-184-17438T>C		intron_variant	Intron 3 of 11		XP_011541691.1
KCNN2	XM_047417166.1	c.-1027-17438T>C		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.-184-17438T>C		intron_variant	Intron 4 of 12	5		ENSP00000427120.4

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121147 AN: 151938 Hom.: 48502 Cov.: 31

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.875

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.971

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.794

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

GnomAD4 genome AF: 0.797 AC: 121255 AN: 152056 Hom.: 48551 Cov.: 31 AF XY: 0.802 AC XY: 59599 AN XY: 74336

African (AFR) AF: 0.741 AC: 30704 AN: 41436

American (AMR) AF: 0.853 AC: 13030 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.759 AC: 2636 AN: 3472

East Asian (EAS) AF: 0.971 AC: 5025 AN: 5174

South Asian (SAS) AF: 0.895 AC: 4313 AN: 4818

European-Finnish (FIN) AF: 0.781 AC: 8258 AN: 10576

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54598 AN: 67992

Other (OTH) AF: 0.796 AC: 1680 AN: 2110

Alfa AF: 0.800 Hom.: 200551

Bravo AF: 0.797

Asia WGS AF: 0.912 AC: 3173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.4
DANN	Benign	0.70
PhyloP100		-0.21

Splicing

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

Other links and lift over

dbSNP: rs36936; hg19: chr5-113679204;