Submissions for variant NM_001271.4(CHD2):c.4173dup (p.Gln1392fs)

dbSNP: rs749969667

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000332337	SCV000329670	pathogenic	not provided	2023-02-17	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 26677509, 31677157, 24614520, 25783594, 26754451, 2578359, 33176815)
Invitae	RCV000202632	SCV001219561	pathogenic	Developmental and epileptic encephalopathy 94	2023-09-10	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln1392Thrfs*17) in the CHD2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHD2 are known to be pathogenic (PMID: 23708187, 24207121). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with childhood-onset epileptic encephalopathy or other photosensitive epileptic syndromes (PMID: 24614520, 25783594, 26754451, 31677157). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 218395). For these reasons, this variant has been classified as Pathogenic.
Génétique des Maladies du Développement, Hospices Civils de Lyon	RCV001251208	SCV001424581	pathogenic	Autistic behavior; Seizure	2020-07-24	criteria provided, single submitter	clinical testing	Frameshift variant absent from gnomAD v3. Several publications. Sanger confirmed.
Institute of Human Genetics, University of Leipzig Medical Center	RCV000202632	SCV002044456	pathogenic	Developmental and epileptic encephalopathy 94	2022-04-01	criteria provided, single submitter	clinical testing	_x000D_ Criteria applied: PVS1, PS2, PS4_MOD
Revvity Omics, Revvity	RCV000202632	SCV003823190	pathogenic	Developmental and epileptic encephalopathy 94	2023-01-30	criteria provided, single submitter	clinical testing
GenomeConnect, ClinGen	RCV000845032	SCV000986868	not provided	CHD2-Related Disorder		no assertion provided	phenotyping only	Variant interpretted as pathogenic and reported on 09/19/2018 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect - Simons Searchlight	RCV001265377	SCV001443502	pathogenic	Complex neurodevelopmental disorder	2019-01-07	no assertion criteria provided	provider interpretation	Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2019-01-07 and interpreted as Pathogenic. Variant was initially reported on 2018-09-19 by GTR ID of laboratory name 26957. The reporting laboratory might also submit to ClinVar.