chr12-75074116-T-C

Variant names:

• chr12-75074116-T-C
• rs2168903
• NM_139137.4:c.688-22799A>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.688-22799A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 151,948 control chromosomes in the GnomAD database, including 2,516 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 0.16 (2516 hom., cov: 31)
• Consequence: KCNC2 NM_139137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362
• Publications: 1 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNC2	NM_139137.4	c.688-22799A>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.688-22799A>G		intron_variant	Intron 2 of 4	1	NM_139137.4	ENSP00000449253.2

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24931 AN: 151832 Hom.: 2500 Cov.: 31

Gnomad AFR AF: 0.0647

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.164 AC: 24955 AN: 151948 Hom.: 2516 Cov.: 31 AF XY: 0.168 AC XY: 12472 AN XY: 74270

African (AFR) AF: 0.0646 AC: 2679 AN: 41440

American (AMR) AF: 0.267 AC: 4076 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 863 AN: 3468

East Asian (EAS) AF: 0.101 AC: 524 AN: 5184

South Asian (SAS) AF: 0.178 AC: 858 AN: 4812

European-Finnish (FIN) AF: 0.249 AC: 2626 AN: 10538

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12600 AN: 67958

Other (OTH) AF: 0.191 AC: 402 AN: 2106

Alfa AF: 0.186 Hom.: 1585

Bravo AF: 0.162

Asia WGS AF: 0.179 AC: 621 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.1
DANN	Benign	0.88
PhyloP100		0.36
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: rs2168903; hg19: chr12-75467896;