9-2729472-AGAC-A
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Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PM4_Supporting
The NM_133497.4(KCNV2):βc.1384_1386delβ(p.Asp462del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,820 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ). Synonymous variant affecting the same amino acid position (i.e. D462D) has been classified as Benign.
Frequency
Genomes: π 0.000026 ( 0 hom., cov: 32)
Exomes π: 6.8e-7 ( 0 hom. )
Consequence
KCNV2
NM_133497.4 inframe_deletion
NM_133497.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.92
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]
PUM3 (HGNC:29676): (pumilio RNA binding family member 3) Enables RNA binding activity. Involved in regulation of protein ADP-ribosylation. Located in chromosome; endoplasmic reticulum; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM1
In a short_sequence_motif Selectivity filter (size 5) in uniprot entity KCNV2_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_133497.4
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_133497.4. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| KCNV2 | NM_133497.4 | c.1384_1386del | p.Asp462del | inframe_deletion | 2/2 | ENST00000382082.4 | NP_598004.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| KCNV2 | ENST00000382082.4 | c.1384_1386del | p.Asp462del | inframe_deletion | 2/2 | 1 | NM_133497.4 | ENSP00000371514 | P1 | |
| PUM3 | ENST00000490444.2 | c.*127-8943_*127-8941del | intron_variant, NMD_transcript_variant | 5 | ENSP00000474467 |
Frequencies
GnomAD3 genomes 0.0000263 AC: 4AN: 152156Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251374Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135856
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461664Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727150
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GnomAD4 genome 0.0000263 AC: 4AN: 152156Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74340
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 18, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 867088). This variant has not been reported in the literature in individuals affected with KCNV2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant, c.1384_1386del, results in the deletion of 1 amino acid(s) of the KCNV2 protein (p.Asp462del), but otherwise preserves the integrity of the reading frame. - |
Retinal dystrophy Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Blueprint Genetics | Feb 07, 2019 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at