chr5-114444490-T-G

Variant names:

• chr5-114444490-T-G
• rs7710366
• NM_021614.4:c.1638-18559T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021614.4(KCNN2):​c.1638-18559T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,758 control chromosomes in the GnomAD database, including 14,667 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 0.41 (14667 hom., cov: 30)
• Consequence: KCNN2 NM_021614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 8 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNN2	NM_021614.4	c.1638-18559T>G		intron_variant	Intron 3 of 7	ENST00000673685.1	NP_067627.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNN2	ENST00000673685.1	c.1638-18559T>G		intron_variant	Intron 3 of 7		NM_021614.4	ENSP00000501239.1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62175 AN: 151640 Hom.: 14669 Cov.: 30

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.410 AC: 62182 AN: 151758 Hom.: 14667 Cov.: 30 AF XY: 0.421 AC XY: 31191 AN XY: 74120

African (AFR) AF: 0.192 AC: 7952 AN: 41380

American (AMR) AF: 0.544 AC: 8292 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1359 AN: 3466

East Asian (EAS) AF: 0.817 AC: 4203 AN: 5142

South Asian (SAS) AF: 0.572 AC: 2748 AN: 4802

European-Finnish (FIN) AF: 0.543 AC: 5694 AN: 10486

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30556 AN: 67910

Other (OTH) AF: 0.404 AC: 852 AN: 2110

Alfa AF: 0.436 Hom.: 8921

Bravo AF: 0.401

Asia WGS AF: 0.644 AC: 2239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		-0.077
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7710366; hg19: chr5-113780187; COSMIC: COSV53285721;