rs17803126

Positions:

• chr12-75183086-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
KCNC2	NM_139137.4	c.687+24211A>G		intron_variant		ENST00000549446.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNC2	ENST00000549446.6	c.687+24211A>G		intron_variant		1	NM_139137.4	P3

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

Gnomad4 AFR AF: 0.0462

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.0965

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0675

Gnomad4 FIN AF: 0.0649

Gnomad4 NFE AF: 0.0909

Gnomad4 OTH AF: 0.0842

Alfa AF: 0.0906 Hom.: 721

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

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

LitVar

Other links and lift over

dbSNP: rs17803126; hg19: chr12-75576866;