5-114444490-T-G

Position:

• chr5-114444490-T-G

Variant summary

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

The NM_021614.4(KCNN2):​c.1638-18559T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,758 control chromosomes in the GnomAD database, including 14,667 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 0.41 (14667 hom., cov: 30)
• Consequence: KCNN2 NM_021614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770

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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNN2	NM_021614.4	c.1638-18559T>G		intron_variant		ENST00000673685.1	NP_067627.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNN2	ENST00000673685.1	c.1638-18559T>G		intron_variant			NM_021614.4	ENSP00000501239	P2

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62175 AN: 151640 Hom.: 14669 Cov.: 30

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.410 AC: 62182 AN: 151758 Hom.: 14667 Cov.: 30 AF XY: 0.421 AC XY: 31191 AN XY: 74120

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.817

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.404

Alfa AF: 0.436 Hom.: 8170

Bravo AF: 0.401

Asia WGS AF: 0.644 AC: 2239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.87

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: rs7710366; hg19: chr5-113780187; COSMIC: COSV53285721;