5-114366537-C-T

Variant names:

• chr5-114366537-C-T
• rs36948
• NM_021614.4:c.1218+2536C>T

Variant summary

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

The NM_021614.4(KCNN2):​c.1218+2536C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,030 control chromosomes in the GnomAD database, including 42,130 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 0.74 (42130 hom., cov: 32)
• Consequence: KCNN2 NM_021614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243
• Publications: 0 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNN2	NM_021614.4	c.1218+2536C>T		intron_variant	Intron 2 of 7	ENST00000673685.1	NP_067627.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNN2	ENST00000673685.1	c.1218+2536C>T		intron_variant	Intron 2 of 7		NM_021614.4	ENSP00000501239.1
KCNN2	ENST00000512097.10	c.1416+2536C>T		intron_variant	Intron 7 of 12	5		ENSP00000427120.4
KCNN2	ENST00000631899.2	c.618+2536C>T		intron_variant	Intron 2 of 8	5		ENSP00000487849.2
KCNN2	ENST00000507750.5	n.249+2536C>T		intron_variant	Intron 2 of 6	3		ENSP00000516687.1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112618 AN: 151912 Hom.: 42078 Cov.: 32

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.970

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.741 AC: 112725 AN: 152030 Hom.: 42130 Cov.: 32 AF XY: 0.745 AC XY: 55362 AN XY: 74318

African (AFR) AF: 0.674 AC: 27944 AN: 41442

American (AMR) AF: 0.798 AC: 12212 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2370 AN: 3468

East Asian (EAS) AF: 0.970 AC: 5022 AN: 5176

South Asian (SAS) AF: 0.820 AC: 3950 AN: 4820

European-Finnish (FIN) AF: 0.723 AC: 7630 AN: 10550

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.751 AC: 51068 AN: 67962

Other (OTH) AF: 0.740 AC: 1563 AN: 2112

Alfa AF: 0.752 Hom.: 5591

Bravo AF: 0.742

Asia WGS AF: 0.887 AC: 3086 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.95
DANN	Benign	0.35
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs36948; hg19: chr5-113702234;