10-101827928-CC-TG

Variant names:

• chr10-101827928-CC-TG
• NM_173191.3:c.662_663delGGinsCA
• KCNIP2 p.Arg221Pro

Variant summary

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

The NM_173191.3(KCNIP2):​c.662_663delGGinsCA​(p.Arg221Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R221Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCNIP2 NM_173191.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.10
• 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]

KCNIP2-AS1 (HGNC:48680): (KCNIP2 antisense RNA 1)

ACMG classification

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

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.662_663delGGinsCA	p.Arg221Pro	missense	N/A	NP_775283.1	Q9NS61-1
	KCNIP2	NM_014591.5		c.707_708delGGinsCA	p.Arg236Pro	missense	N/A	NP_055406.2
	KCNIP2	NM_173192.3		c.608_609delGGinsCA	p.Arg203Pro	missense	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.662_663delGGinsCA	p.Arg221Pro	missense	N/A	ENSP00000349055.2	Q9NS61-1
	KCNIP2	ENST00000461105.5	TSL:1	c.707_708delGGinsCA	p.Arg236Pro	missense	N/A	ENSP00000420040.1	Q9NS61-6
	KCNIP2	ENST00000358038.7	TSL:1	c.608_609delGGinsCA	p.Arg203Pro	missense	N/A	ENSP00000350733.3	Q9NS61-2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-103587685;