10-101829858-C-T

Variant names:

• chr10-101829858-C-T
• rs929916944
• NM_173191.3:c.209G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173191.3(KCNIP2):​c.209G>A​(p.Arg70His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000417 in 1,487,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 26)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: KCNIP2 NM_173191.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30
• Publications: 0 publications found

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]

ENSG00000308219 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16344163).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173191.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNIP2	NM_173191.3	MANE Select	c.209G>A	p.Arg70His	missense	Exon 3 of 10	NP_775283.1	Q9NS61-1
	KCNIP2	NM_014591.5		c.254G>A	p.Arg85His	missense	Exon 3 of 10	NP_055406.2
	KCNIP2	NM_173192.3		c.170-659G>A		intron	N/A	NP_775284.1	Q9NS61-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNIP2	ENST00000356640.7	TSL:1 MANE Select	c.209G>A	p.Arg70His	missense	Exon 3 of 10	ENSP00000349055.2	Q9NS61-1
	KCNIP2	ENST00000461105.5	TSL:1	c.254G>A	p.Arg85His	missense	Exon 3 of 10	ENSP00000420040.1	Q9NS61-6
	KCNIP2	ENST00000358038.7	TSL:1	c.170-659G>A		intron	N/A	ENSP00000350733.3	Q9NS61-2

Frequencies

GnomAD3 genomes AF: 0.0000200 AC: 3 AN: 150096 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.0000247

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000664

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000284 AC: 3 AN: 105564 AF XY: 0.0000174

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000695

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000441 AC: 59 AN: 1337692 Hom.: 0 Cov.: 32 AF XY: 0.0000440 AC XY: 29 AN XY: 659622

African (AFR) AF: 0.00 AC: 0 AN: 26884

American (AMR) AF: 0.00 AC: 0 AN: 21178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22948

East Asian (EAS) AF: 0.0000972 AC: 3 AN: 30866

South Asian (SAS) AF: 0.00 AC: 0 AN: 71152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5460

European-Non Finnish (NFE) AF: 0.0000463 AC: 49 AN: 1057402

Other (OTH) AF: 0.000127 AC: 7 AN: 55312

GnomAD4 genome AF: 0.0000200 AC: 3 AN: 150096 Hom.: 0 Cov.: 26 AF XY: 0.0000273 AC XY: 2 AN XY: 73144

African (AFR) AF: 0.0000247 AC: 1 AN: 40552

American (AMR) AF: 0.0000664 AC: 1 AN: 15062

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5092

South Asian (SAS) AF: 0.00 AC: 0 AN: 4618

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67622

Other (OTH) AF: 0.00 AC: 0 AN: 2046

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Benign	0.93
DEOGEN2	Benign	0.099	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.76	N
PhyloP100		1.3
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.024
Sift	Benign	0.18	T
Sift4G	Benign	0.21	T
Polyphen		0.48	P
Vest4		0.24
MutPred		0.24		Loss of methylation at R65 (P = 0.0735)
MVP		0.68
MPC		0.81
ClinPred		0.21	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		3.2
Varity_R		0.081
gMVP		0.44
Mutation Taster		=89/11	polymorphism

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: rs929916944; hg19: chr10-103589615;