5-114362934-T-TGCC

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BA1

The NM_021614.4(KCNN2):c.807_809dup(p.Ala269dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 1,560,626 control chromosomes in the GnomAD database, including 169,803 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (16051 hom., cov: 0)
  • Exomes 𝑓: 0.46 (153752 hom.)
• Consequence: KCNN2 NM_021614.4 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.23

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 -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_021614.4
• BP6: Variant 5-114362934-T-TGCC is Benign according to our data. Variant chr5-114362934-T-TGCC is described in ClinVar as [Benign]. Clinvar id is 769655.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNN2	NM_021614.4	c.807_809dup	p.Ala269dup	inframe_insertion	1/8	ENST00000673685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNN2	ENST00000673685.1	c.807_809dup	p.Ala269dup	inframe_insertion	1/8		NM_021614.4	P2
KCNN2	ENST00000512097.10	c.1005_1007dup	p.Ala335dup	inframe_insertion	6/13	5		A2
KCNN2	ENST00000631899.2	c.209_211dup	p.Ala70dup	inframe_insertion	1/9	5

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68122 AN: 150628 Hom.: 16047 Cov.: 0

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.860

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.431

GnomAD3 exomes AF: 0.470 AC: 83199 AN: 176860 Hom.: 21049 AF XY: 0.469 AC XY: 45906 AN XY: 97952

Gnomad AFR exome AF: 0.304

Gnomad AMR exome AF: 0.523

Gnomad ASJ exome AF: 0.451

Gnomad EAS exome AF: 0.833

Gnomad SAS exome AF: 0.548

Gnomad FIN exome AF: 0.419

Gnomad NFE exome AF: 0.404

Gnomad OTH exome AF: 0.447

GnomAD4 exome AF: 0.461 AC: 650031 AN: 1409886 Hom.: 153752 Cov.: 34 AF XY: 0.464 AC XY: 324368 AN XY: 699704

Gnomad4 AFR exome AF: 0.355

Gnomad4 AMR exome AF: 0.524

Gnomad4 ASJ exome AF: 0.459

Gnomad4 EAS exome AF: 0.864

Gnomad4 SAS exome AF: 0.569

Gnomad4 FIN exome AF: 0.471

Gnomad4 NFE exome AF: 0.440

Gnomad4 OTH exome AF: 0.467

GnomAD4 genome AF: 0.452 AC: 68145 AN: 150740 Hom.: 16051 Cov.: 0 AF XY: 0.460 AC XY: 33819 AN XY: 73586

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.860

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.433

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 12, 2019

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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: rs111266015; hg19: chr5-113698631;