Novel genetic risk variants for pediatric celiac disease

Balasopoulou, Angeliki; Stanković, Biljana; Panagiotara, Angeliki; Nikčevic, Gordana; Peters, Brock A.; John, Anne; Mendrinou, Effrosyni; Stratopoulos, Apostolos; Legaki, Aigli Ioanna; Stathakopoulou, Vasiliki; Tsolia, Aristoniki; Govaris, Nikolaos; Govari, Sofia; Zagoriti, Zoi; Poulas, Konstantinos; Kanariou, Maria; Constantinidou, Nikki; Krini, Maro; Spanou, Kleopatra; Radlovic, Nedeljko; Ali, Bassam R.; Borg, Joseph; Drmanac, Radoje; Chrousos, George; Pavlovic, Sonja; Roma, Eleftheria; Zukic, Branka; Patrinos, George P.; Katsila, Theodora

doi:10.1186/s40246-016-0091-1

Human Genomics

Table 1 In silico analyses outcome of the six variants of prime interest identified in the family trio

From: Novel genetic risk variants for pediatric celiac disease

HUGO gene symbol	HGVS description of variant	AA position	Reference residue	Alternative residue	PROVEAN prediction			SIFT prediction		Variant effect predictor
HUGO gene symbol	HGVS description of variant	AA position	Reference residue	Alternative residue	Variation type	Score	Prediction	Score	Prediction	Consequence	Impact	PolyPhen	LoFtool
SLC9A4	c.1919G>A	640	R	K	Single AA change	−0.67	Neutral	0.140	Tolerated	Frameshift variant	High	–	0.911
NCK2	c.745_746delAAinsG	249	K	E	Single AA change	−1.97	Neutral	0.010	Damaging	Frameshift variant	High	–	0.223
HOXD12	c.418G>A	140	A	T	Single AA change	−0.01	Neutral	0.201	Tolerated	Frameshift variant	High	–	0.432
KIAA1109	c.2933T>C	978	I	T	Single AA change	−0.25	Neutral	0.187	Tolerated	Frameshift variant	High	–	0.845
KIAA1109	c.4268_4269delCCinsTA	1423	T	I	Single AA change	−1.22	Neutral	0.108	Tolerated	Missense variant	Moderate	Benign (0.031)	0.845
HOXB6	c.668C>A	223	A	D	Single AA change	−.029	Neutral	0.230	Tolerated	Frameshift variant	High	–	–

Source: PROVEAN v1.1.3 (PROVEAN human genome variants tool, http://provean.jcvi.org/genome_submit_2.php?species=human) and Variant Effect Predictor (http://grch37.ensembl.org/Homo_sapiens/Tools/VEP). Assembly: GRCh37. PROVEAN introduces a delta alignment score based on the reference and variant versions of a protein query sequence with respect to sequence homologs (NCBI NR protein database through BLAST, http://www.ncbi.nlm.nih.gov/). The default score threshold was set at −2.5 for binary classification (deleterious <−2.5 vs. neutral > −2.5). Similarly, (through PSI-BLAST, http://blast.ncbi.nlm.nih.gov/Blast.cgi?CMD=Web&PAGE=Proteins&PROGRAM=blastp&RUN_PSIBLAST=on), SIFT (http://sift.jcvi.org/) may be applied to naturally occurring non-synonymous variants. SIFT score ranges from 0 to 1. A SIFT score of ≤0.05 corresponds to a “damaging” prediction, whereas a SIFT score >0.05 predicts that the variant is likely to be “tolerated.” VEP; Consequence—consequence type of this variation, Impact—a subjective classification of the severity of the variant consequence (high: the variant is assumed to have disruptive impact in the protein, probably causing protein truncation or loss of function or triggering nonsense mediated decay, moderate: a non-disruptive variant that might change protein effectiveness, low: assumed to be mostly harmless or unlikely to change protein behavior, modifier: usually non-coding variants affecting non-coding genes, where predictions are difficult or there is no evidence of impact), PolyPhen—the PolyPhen prediction and/or score, LoFtool—provides a per-gene rank of genic intolerance and consequent susceptibility to disease based on the ratio of loss of function (LoF) to synonymous mutations in ExAC data

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ISSN: 1479-7364

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