Submissions for variant NM_007254.4(PNKP):c.1322C>G (p.Ala441Gly)

gnomAD frequency: 0.00003  dbSNP: rs549000007

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001721212	SCV000242070	likely benign	not provided	2019-02-18	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27081543)
Invitae	RCV000226268	SCV000289721	benign	Developmental and epileptic encephalopathy, 12	2024-01-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002314738	SCV000848434	benign	Inborn genetic diseases	2019-03-18	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Eurofins Ntd Llc (ga)	RCV000188456	SCV000858864	likely benign	not specified	2018-01-10	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001131823	SCV001291460	likely benign	Microcephaly, seizures, and developmental delay	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Genetic Services Laboratory, University of Chicago	RCV000188456	SCV002065979	benign	not specified	2021-11-16	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001721212	SCV004140472	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	PNKP: BS1