chr11-66261916-C-G
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001318734.2(KLC2):āc.403C>Gā(p.Gln135Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000279 in 1,614,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00012 ( 0 hom., cov: 32)
Exomes š: 0.000018 ( 0 hom. )
Consequence
KLC2
NM_001318734.2 missense
NM_001318734.2 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 6.65
Genes affected
KLC2 (HGNC:20716): (kinesin light chain 2) The protein encoded by this gene is a light chain of kinesin, a molecular motor responsible for moving vesicles and organelles along microtubules. Defects in this gene are a cause of spastic paraplegia, optic atrophy, and neuropathy (SPOAN) syndrome. [provided by RefSeq, Mar 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06580135).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KLC2 | NM_001318734.2 | c.403C>G | p.Gln135Glu | missense_variant | 3/16 | ENST00000394067.7 | NP_001305663.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KLC2 | ENST00000394067.7 | c.403C>G | p.Gln135Glu | missense_variant | 3/16 | 1 | NM_001318734.2 | ENSP00000377631 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152208Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251228Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135834
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GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461858Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727226
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GnomAD4 genome AF: 0.000118 AC: 18AN: 152326Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74484
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 19, 2022 | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 135 of the KLC2 protein (p.Gln135Glu). This variant is present in population databases (rs150052320, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with KLC2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
T;T;.;T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;.;.;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.;N;N;.;.
MutationTaster
Benign
D;D;D;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;D;D;T;T;T;D
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
B;.;.;B;B;B;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at