rs17803126

Variant names:

• chr12-75183086-T-C
• rs17803126
• NM_139137.4:c.687+24211A>G

Variant summary

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

The NM_139137.4(KCNC2):​c.687+24211A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0784 in 152,308 control chromosomes in the GnomAD database, including 538 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 0.078 (538 hom., cov: 32)
• Consequence: KCNC2 NM_139137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 4 publications found

Genes affected

KCNC2 (HGNC:6234): (potassium voltage-gated channel subfamily C member 2) The Shaker gene family of Drosophila encodes components of voltage-gated potassium channels and is comprised of four subfamilies. Based on sequence similarity, this gene is similar to one of these subfamilies, namely the Shaw subfamily. The protein encoded by this gene belongs to the delayed rectifier class of channel proteins and is an integral membrane protein that mediates the voltage-dependent potassium ion permeability of excitable membranes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

KCNC2 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy 103

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNC2	NM_139137.4	c.687+24211A>G		intron_variant	Intron 2 of 4	ENST00000549446.6	NP_631875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNC2	ENST00000549446.6	c.687+24211A>G		intron_variant	Intron 2 of 4	1	NM_139137.4	ENSP00000449253.2

Frequencies

GnomAD3 genomes AF: 0.0784 AC: 11929 AN: 152190 Hom.: 538 Cov.: 32

Gnomad AFR AF: 0.0461

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0671

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0909

Gnomad OTH AF: 0.0851

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

GnomAD4 genome AF: 0.0784 AC: 11941 AN: 152308 Hom.: 538 Cov.: 32 AF XY: 0.0772 AC XY: 5747 AN XY: 74482

African (AFR) AF: 0.0462 AC: 1920 AN: 41580

American (AMR) AF: 0.140 AC: 2146 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0965 AC: 335 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5180

South Asian (SAS) AF: 0.0675 AC: 326 AN: 4828

European-Finnish (FIN) AF: 0.0649 AC: 690 AN: 10624

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0909 AC: 6182 AN: 68018

Other (OTH) AF: 0.0842 AC: 178 AN: 2114

Alfa AF: 0.0902 Hom.: 905

Bravo AF: 0.0841

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.62
PhyloP100		0.16
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: rs17803126; hg19: chr12-75576866;