Variant 10-101829113-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_173191.3(KCNIP2):c.310C>T(p.Arg104Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,614,164 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 2 hom. )

Consequence

KCNIP2
NM_173191.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.77

Variant links:

Genes affected

KCNIP2 (HGNC:15522): (potassium voltage-gated channel interacting protein 2) This gene encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), which belongs to the recoverin branch of the EF-hand superfamily. Members of the KCNIP family are small calcium binding proteins. They all have EF-hand-like domains, and differ from each other in the N-terminus. They are integral subunit components of native Kv4 channel complexes. They may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified from this gene. [provided by RefSeq, Jul 2008]

KCNIP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06509718).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNIP2	NM_173191.3 linkuse as main transcript	c.310C>T	p.Arg104Cys	missense_variant	4/10	ENST00000356640.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNIP2	ENST00000356640.7 linkuse as main transcript	c.310C>T	p.Arg104Cys	missense_variant	4/10	1	NM_173191.3		Q9NS61-1

Frequencies

GnomAD3 genomes

AF:

0.000493

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000521

AC:

131

AN:

251352

Hom.:

AF XY:

0.000537

AC XY:

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.00102

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.00111

AC:

1625

AN:

1461848

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

803

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.00139

Gnomad4 OTH exome

AF:

0.000927

GnomAD4 genome

AF:

0.000492

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000903

Hom.:

Bravo

AF:

0.000544

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000576

AC:

EpiCase

AF:

0.00131

EpiControl

AF:

0.000711

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.355C>T (p.R119C) alteration is located in exon 4 (coding exon 4) of the KCNIP2 gene. This alteration results from a C to T substitution at nucleotide position 355, causing the arginine (R) at amino acid position 119 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.61

.;.;D;.;.;.;.;.

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.098

FATHMM_MKL

Benign

0.62

LIST_S2

Pathogenic

0.98

D;D;D;D;D;D;D;D

M_CAP

Benign

0.033

MetaRNN

Benign

0.065

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.7

.;.;M;.;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-5.3

D;D;D;D;.;D;D;D

REVEL

Benign

0.13

Sift

Pathogenic

0.0

D;D;D;D;.;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D;.;D;D;D

Polyphen

0.99, 0.99, 0.98, 0.74, 0.84

.;D;D;.;.;D;P;P

Vest4

0.51

MVP

0.37

MPC

1.7

ClinPred

0.17

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.53

gMVP

0.52

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over