rs1554628460

Variant names:

• chr9-2717843-C-CCCGTTCCGGCTCCCAGGCCAGCATCCACGGCTGGACAGAGGGCAACTATAACTACTACATCGAGGAAGACGAAGACGGCGAGGAGGAGGACCAGTGGAAGGACGACCTGGCAGAAGAGGACCAGCAGGCAGGGGAGGTCACCACCGCCAAGCCCGAGGGCCCCAGCGACCCTCCGGCCCTGCTGT
• rs1554628460
• NM_133497.4:c.107_291dupGTTCCGGCTCCCAGGCCAGCATCCACGGCTGGACAGAGGGCAACTATAACTACTACATCGAGGAAGACGAAGACGGCGAGGAGGAGGACCAGTGGAAGGACGACCTGGCAGAAGAGGACCAGCAGGCAGGGGAGGTCACCACCGCCAAGCCCGAGGGCCCCAGCGACCCTCCGGCCCTGCTGTCC

Variant summary

Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PVS1 PP5

The NM_133497.4(KCNV2):​c.107_291dupGTTCCGGCTCCCAGGCCAGCATCCACGGCTGGACAGAGGGCAACTATAACTACTACATCGAGGAAGACGAAGACGGCGAGGAGGAGGACCAGTGGAAGGACGACCTGGCAGAAGAGGACCAGCAGGCAGGGGAGGTCACCACCGCCAAGCCCGAGGGCCCCAGCGACCCTCCGGCCCTGCTGTCC​(p.Thr98ValfsTer64) variant causes a frameshift 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 INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. T98T) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KCNV2 NM_133497.4 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -0.572
• Publications: 0 publications found

Genes affected

KCNV2 (HGNC:19698): (potassium voltage-gated channel modifier subfamily V member 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 voltage-gated channel subfamily V. This member is identified as a 'silent subunit', and it does not form homomultimers, but forms heteromultimers with several other subfamily members. Through obligatory heteromerization, it exerts a function-altering effect on other potassium channel subunits. This protein is strongly expressed in pancreas and has a weaker expression in several other tissues. [provided by RefSeq, Jul 2008]

KCNV2 Gene-Disease associations (from GenCC):

• cone dystrophy with supernormal rod response

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• inherited retinal dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ENSG00000286670 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 9 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant 9-2717843-C-CCCGTTCCGGCTCCCAGGCCAGCATCCACGGCTGGACAGAGGGCAACTATAACTACTACATCGAGGAAGACGAAGACGGCGAGGAGGAGGACCAGTGGAAGGACGACCTGGCAGAAGAGGACCAGCAGGCAGGGGAGGTCACCACCGCCAAGCCCGAGGGCCCCAGCGACCCTCCGGCCCTGCTGT is Pathogenic according to our data. Variant chr9-2717843-C-CCCGTTCCGGCTCCCAGGCCAGCATCCACGGCTGGACAGAGGGCAACTATAACTACTACATCGAGGAAGACGAAGACGGCGAGGAGGAGGACCAGTGGAAGGACGACCTGGCAGAAGAGGACCAGCAGGCAGGGGAGGTCACCACCGCCAAGCCCGAGGGCCCCAGCGACCCTCCGGCCCTGCTGT is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 438243.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133497.4. 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
	KCNV2	NM_133497.4	MANE Select	c.107_291dupGTTCCGGCTCCCAGGCCAGCATCCACGGCTGGACAGAGGGCAACTATAACTACTACATCGAGGAAGACGAAGACGGCGAGGAGGAGGACCAGTGGAAGGACGACCTGGCAGAAGAGGACCAGCAGGCAGGGGAGGTCACCACCGCCAAGCCCGAGGGCCCCAGCGACCCTCCGGCCCTGCTGTCC	p.Thr98ValfsTer64	frameshift	Exon 1 of 2	NP_598004.1	Q8TDN2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNV2	ENST00000382082.4	TSL:1 MANE Select	c.107_291dupGTTCCGGCTCCCAGGCCAGCATCCACGGCTGGACAGAGGGCAACTATAACTACTACATCGAGGAAGACGAAGACGGCGAGGAGGAGGACCAGTGGAAGGACGACCTGGCAGAAGAGGACCAGCAGGCAGGGGAGGTCACCACCGCCAAGCCCGAGGGCCCCAGCGACCCTCCGGCCCTGCTGTCC	p.Thr98ValfsTer64	frameshift	Exon 1 of 2	ENSP00000371514.3	Q8TDN2
	ENSG00000286670	ENST00000768783.1		n.113+28270_113+28454dupACAGCAGGGCCGGAGGGTCGCTGGGGCCCTCGGGCTTGGCGGTGGTGACCTCCCCTGCCTGCTGGTCCTCTTCTGCCAGGTCGTCCTTCCACTGGTCCTCCTCCTCGCCGTCTTCGTCTTCCTCGATGTAGTAGTTATAGTTGCCCTCTGTCCAGCCGTGGATGCTGGCCTGGGAGCCGGAACGG		intron	N/A
	ENSG00000286670	ENST00000768784.1		n.156+13917_156+14101dupACAGCAGGGCCGGAGGGTCGCTGGGGCCCTCGGGCTTGGCGGTGGTGACCTCCCCTGCCTGCTGGTCCTCTTCTGCCAGGTCGTCCTTCCACTGGTCCTCCTCCTCGCCGTCTTCGTCTTCCTCGATGTAGTAGTTATAGTTGCCCTCTGTCCAGCCGTGGATGCTGGCCTGGGAGCCGGAACGG		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 68

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.57

Splicing

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

Other links and lift over

dbSNP: rs1554628460; hg19: chr9-2717843;