rs1242600338

Variant names:

• chr5-114362558-GGCAGCAGTACGC-G
• rs1242600338
• NM_021614.4:c.428_439delACGCGCAGCAGT

Your query was ambiguous. Multiple possible variants found:

• chr5-114362558-GGCAGCAGTACGC-G
• chr5-114362558-GGCAGCAGTACGC-GGCAGCAGTACGCGCAGCAGTACGC

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4 BS2

The NM_021614.4(KCNN2):​c.428_439delACGCGCAGCAGT​(p.Tyr143_Gln146del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000391 in 460,938 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: not found (cov: 33)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: KCNN2 NM_021614.4 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.06

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 -2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_021614.4.
• BS2: High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNN2	NM_021614.4	c.428_439delACGCGCAGCAGT	p.Tyr143_Gln146del	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.428_439delACGCGCAGCAGT	p.Tyr143_Gln146del	disruptive_inframe_deletion	Exon 1 of 8		NM_021614.4	ENSP00000501239.1
KCNN2	ENST00000512097.10	c.626_637delACGCGCAGCAGT	p.Tyr209_Gln212del	disruptive_inframe_deletion	Exon 6 of 13	5		ENSP00000427120.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000391 AC: 18 AN: 460938 Hom.: 0 AF XY: 0.0000292 AC XY: 7 AN XY: 239774

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000800

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000266

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000228

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1242600338; hg19: chr5-113698255;