Clinical foetal exome (WES) (proband)

Test covered by the reimbursement:

YES

Test without reimbursement:

YES

Gender:

Woman

Material:

Chorionic villi, Amniotic fluid …

Turnover time:

6 months

STATIM:

1 month

Material:

Chorionic villi | Chorionic villi, min. 30 mg tissue in a microtube (Eppendorf type)

Storage after examination: week after the report is issued 2 – 8°C

Amniotic fluid | 3x 10 ml of amniotic fluid in a tube

Storage after examination: week after the report is issued 2 – 8°C

Cord blood | 2–3 ml of cord blood in EDTA

Storage after examination: week after the report is issued 2 – 8°C

Isolated DNA from chorionic villi | 30–100 ng/μL of isolated DNA from chorionic villi in a microtube (Eppendorf type)

Storage after examination: stored in a DNA archive without restriction 15°C

Isolated DNA from amniotic fluid | 30–100 ng/μL of isolated DNA from amniocentesis in a microtube (Eppendorf type)

Storage after examination: stored in a DNA archive without restriction 15°C

Isolated DNA from cordocentesis | 30–100 ng/μL of isolated DNA from cordocentesis in a microtube (Eppendorf type)

Storage after examination: stored in a DNA archive without restriction 15°C

Cultured cells | 1.5 ml of cultured cells in a microtube (Eppendorf type)

Storage after examination: 180 days 2 – 8°C

DNA isolated from cultured cells | 30–100 ng/μL of isolated DNA from cultured cells in a microtube (Eppendorf type)

Storage after examination: stored in the DNA archive 15°C

Quick test description:

NGS analysis of exome (WES) and other clinically relevant regions of the foetal genome; we recommend simultaneously performing exome analysis also in the parents of the foetus – so-called trio analysis.

Test details:

The clinical exome is tested by massively parallel sequencing on the Illumina platform (NovaSeq Xplus) from whole-exome sequencing (WES) data using virtual panels. The testing includes an analysis identifying potentially causal variants according to phenotype-dependent prioritisation for given models of inheritance of the family tested. A minimum sequencing depth of 30x is achieved at >98% of target regions. The obtained data are analysed according to our own bioinformatic evaluation, which includes mapping to the GRCh38 genome reference sequence, variant calling, annotation with the current version of Ensembl and filtering of clinically significant variants according to a number of annotation outputs from population, clinical and prediction databases. Each of the above steps is supplemented by quality control.

Intron variants are assessed for the effect on pre-mRNA splicing in the range of +/- 15bp from the exon boundary. Variants in 5' and 3' UTR regions are reported if there is evidence of their pathogenic impact in clinical databases. Results are reported only in samples that have passed bioinformatic quality control (e.g. phred score quality, depth of sequencing, uniformity of coverage).

The clinical interpretation of genetic variants detected is performed by experts based on the indication for testing, a review of relevant scientific literature, external databases, our internal clinical genetic database and the manual checking of sequencing data. All available evidence of identified variants was classified according to the MGL Gennet Variant Interpretation Procedure based on IACR**** standards, ACMG guidelines (PMID: 25741868) and specifying procedures (PMID: 28492532, doi: 10.1136/jmedgenet-2020-107248) and HGVS genetic nomenclature. The clinical significance status of the ClinVar database is periodically checked with the release of a new version of Ensembl. For patients whose pathogenicity classification was changed (to class 4/5) with the release of a new version of the database, we issue an updated laboratory report. The laboratory report also incudes incidental findings of pathogenic and probably pathogenic variants (class 4 and 5) in genes according to ACMG (PMID: 27854360) guidelines, in tumour predisposition genes reported by our laboratory as part of the CZECANCA testing, and in genes reported by our laboratory as part of the CarrierTest.

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