5-114362471-CCTGCTG-CCTG

Variant names:

• chr5-114362471-CCTG-C
• rs567706065
• NM_021614.4:c.350_352delGCT

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM4_Supporting BS2

The NM_021614.4(KCNN2):​c.350_352delGCT​(p.Cys117del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00823 in 428,952 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.013 (0 hom.)
• Consequence: KCNN2 NM_021614.4 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77

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 Likely_benign. Variant got -3 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_021614.4. Strenght limited to Supporting due to length of the change: 1aa.
• BS2: High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNN2	NM_021614.4	c.350_352delGCT	p.Cys117del	disruptive_inframe_deletion	Exon 1 of 8	ENST00000673685.1	NP_067627.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNN2	ENST00000673685.1	c.350_352delGCT	p.Cys117del	disruptive_inframe_deletion	Exon 1 of 8		NM_021614.4	ENSP00000501239.1
KCNN2	ENST00000512097.10	c.548_550delGCT	p.Cys183del	disruptive_inframe_deletion	Exon 6 of 13	5		ENSP00000427120.4

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152034 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0127 AC: 3515 AN: 276918 Hom.: 0 AF XY: 0.0129 AC XY: 1863 AN XY: 144072

Gnomad4 AFR exome AF: 0.0116

Gnomad4 AMR exome AF: 0.0122

Gnomad4 ASJ exome AF: 0.0126

Gnomad4 EAS exome AF: 0.0118

Gnomad4 SAS exome AF: 0.0146

Gnomad4 FIN exome AF: 0.0119

Gnomad4 NFE exome AF: 0.0129

Gnomad4 OTH exome AF: 0.0111

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152034 Hom.: 0 Cov.: 33 AF XY: 0.0000943 AC XY: 7 AN XY: 74254

Gnomad4 AFR AF: 0.000386

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000907

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs567706065; hg19: chr5-113698168;