rs2974490

Positions:

• chr5-114070179-G-A
• chr5-114070179-G-C
• chr5-114070179-G-T

Variant summary

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

The NM_001372233.1(KCNN2):​c.-340+13008G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 152,156 control chromosomes in the GnomAD database, including 58,208 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 0.87 (58208 hom., cov: 31)
• Consequence: KCNN2 NM_001372233.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNN2	NM_001372233.1	c.-340+13008G>A		intron_variant			NP_001359162.1
KCNN2	XM_011543389.2	c.-271+13008G>A		intron_variant			XP_011541691.1
KCNN2	XM_047417166.1	c.-1183+13008G>A		intron_variant			XP_047273122.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNN2	ENST00000512097.10	c.-340+13008G>A		intron_variant		5		ENSP00000427120	A2
KCNN2	ENST00000512927.2	n.647+13008G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132805 AN: 152038 Hom.: 58159 Cov.: 31

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.930

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.901

Gnomad OTH AF: 0.867

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

GnomAD4 genome AF: 0.873 AC: 132908 AN: 152156 Hom.: 58208 Cov.: 31 AF XY: 0.871 AC XY: 64757 AN XY: 74382

Gnomad4 AFR AF: 0.870

Gnomad4 AMR AF: 0.797

Gnomad4 ASJ AF: 0.844

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.844

Gnomad4 FIN AF: 0.930

Gnomad4 NFE AF: 0.901

Gnomad4 OTH AF: 0.866

Alfa AF: 0.871 Hom.: 5472

Bravo AF: 0.860

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.091
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2974490; hg19: chr5-113405876;