NM_021614.4:c.1638-18559T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0770

Publications

8 publications found
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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
KCNN2NM_021614.4 linkc.1638-18559T>G intron_variant Intron 3 of 7 ENST00000673685.1 NP_067627.3 Q9H2S1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KCNN2ENST00000673685.1 linkc.1638-18559T>G intron_variant Intron 3 of 7 NM_021614.4 ENSP00000501239.1 A0A669KBH3

Frequencies

GnomAD3 genomes
AF:
0.410
AC:
62175
AN:
151640
Hom.:
14669
Cov.:
30
show subpopulations
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
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
1684
3367
5051
6734
8418
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
588
1176
1764
2352
2940
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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

Publications

Other links and lift over

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