5-114070179-G-A

Variant names:

• chr5-114070179-G-A
• rs2974490
• NM_001372233.1:c.-340+13008G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

KCNN2 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with or without variable movement or behavioral abnormalities

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KCNN2	NM_001372233.1	c.-340+13008G>A		intron_variant	Intron 2 of 12		NP_001359162.1
KCNN2	XM_011543389.2	c.-271+13008G>A		intron_variant	Intron 2 of 11		XP_011541691.1
KCNN2	XM_047417166.1	c.-1183+13008G>A		intron_variant	Intron 2 of 11		XP_047273122.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNN2	ENST00000512097.10	c.-340+13008G>A		intron_variant	Intron 2 of 12	5		ENSP00000427120.4
KCNN2	ENST00000512927.2	n.647+13008G>A		intron_variant	Intron 2 of 4	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

African (AFR) AF: 0.870 AC: 36096 AN: 41494

American (AMR) AF: 0.797 AC: 12193 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2926 AN: 3468

East Asian (EAS) AF: 0.705 AC: 3628 AN: 5144

South Asian (SAS) AF: 0.844 AC: 4062 AN: 4812

European-Finnish (FIN) AF: 0.930 AC: 9872 AN: 10612

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.901 AC: 61254 AN: 68006

Other (OTH) AF: 0.866 AC: 1830 AN: 2114

Alfa AF: 0.870 Hom.: 5763

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
PhyloP100		-2.2

Splicing

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

Other links and lift over

dbSNP: rs2974490; hg19: chr5-113405876;