Submissions for variant NM_007254.4(PNKP):c.831G>A (p.Thr277=)

gnomAD frequency: 0.00128  dbSNP: rs148491228

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000147370	SCV000113446	likely benign	not specified	2017-05-24	criteria provided, single submitter	clinical testing
GeneDx	RCV000147370	SCV000171056	benign	not specified	2013-06-10	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Genetic Services Laboratory, University of Chicago	RCV000147370	SCV000194747	likely benign	not specified	2014-02-27	criteria provided, single submitter	clinical testing
Invitae	RCV000229790	SCV000289725	likely benign	Developmental and epileptic encephalopathy, 12	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000147370	SCV000311777	likely benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000319452	SCV000414348	uncertain significance	Microcephaly, seizures, and developmental delay	2018-01-12	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Ambry Genetics	RCV002313784	SCV000848096	likely benign	Inborn genetic diseases	2016-07-01	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
CeGaT Center for Human Genetics Tuebingen	RCV001171811	SCV001334676	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	PNKP: BP4, BP7
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001171811	SCV001930232	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001171811	SCV001964745	likely benign	not provided		no assertion criteria provided	clinical testing