chr10-101831124-G-T

Position:

• chr10-101831124-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173191.3(KCNIP2):​c.117C>A​(p.Phe39Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCNIP2 NM_173191.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.28

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30272186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNIP2	NM_173191.3	c.117C>A	p.Phe39Leu	missense_variant	2/10	ENST00000356640.7	NP_775283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNIP2	ENST00000356640.7	c.117C>A	p.Phe39Leu	missense_variant	2/10	1	NM_173191.3	ENSP00000349055.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 14, 2023

The c.117C>A (p.F39L) alteration is located in exon 2 (coding exon 2) of the KCNIP2 gene. This alteration results from a C to A substitution at nucleotide position 117, causing the phenylalanine (F) at amino acid position 39 to be replaced by a leucine (L). 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	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	.;T;.
Eigen	Benign	-0.026
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	0.61	N;N;N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.38	N;N;N
REVEL	Benign	0.075
Sift	Benign	0.32	T;T;T
Sift4G	Benign	0.91	T;T;T
Polyphen		0.0	B;B;P
Vest4		0.42
MutPred		0.34		Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);
MVP		0.87
MPC		0.78
ClinPred		0.92	D
GERP RS		4.9
Varity_R		0.29
gMVP		0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-103590881;