21-34364464-T-C

Variant names:

• chr21-34364464-T-C
• rs117961635
• NM_172201.2:c.-13+313T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_172201.2(KCNE2):​c.-13+313T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0059 in 152,212 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0059 (4 hom., cov: 32)
• Consequence: KCNE2 NM_172201.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0230

Genes affected

KCNE2 (HGNC:6242): (potassium voltage-gated channel subfamily E regulatory subunit 2) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, isk-related subfamily. This member is a small integral membrane subunit that assembles with the KCNH2 gene product, a pore-forming protein, to alter its function. This gene is expressed in heart and muscle and the gene mutations are associated with cardiac arrhythmia. [provided by RefSeq, Jul 2008]

ENSG00000225555 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 21-34364464-T-C is Benign according to our data. Variant chr21-34364464-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1188351.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 898 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNE2	NM_172201.2	c.-13+313T>C		intron_variant	Intron 1 of 1	ENST00000290310.4	NP_751951.1
LOC105372791	NR_188571.1	n.852+5971A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNE2	ENST00000290310.4	c.-13+313T>C		intron_variant	Intron 1 of 1	1	NM_172201.2	ENSP00000290310.2
KCNE2	ENST00000715813.1	c.-10+313T>C		intron_variant	Intron 5 of 5			ENSP00000520524.1
ENSG00000225555	ENST00000440403.2	n.854+5971A>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.00590 AC: 898 AN: 152094 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000941

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.0246

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00628

Gnomad OTH AF: 0.00862

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

GnomAD4 genome AF: 0.00590 AC: 898 AN: 152212 Hom.: 4 Cov.: 32 AF XY: 0.00645 AC XY: 480 AN XY: 74434

African (AFR) AF: 0.000939 AC: 39 AN: 41554

American (AMR) AF: 0.00157 AC: 24 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0288 AC: 100 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00601 AC: 29 AN: 4828

European-Finnish (FIN) AF: 0.0246 AC: 261 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00628 AC: 427 AN: 68000

Other (OTH) AF: 0.00853 AC: 18 AN: 2110

Alfa AF: 0.00623 Hom.: 1

Bravo AF: 0.00366

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 15, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.69
PhyloP100		-0.023
PromoterAI		-0.0064	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Other links and lift over

dbSNP: rs117961635; hg19: chr21-35736763;