Submissions for variant NM_031263.4(HNRNPK):c.253G>A (p.Glu85Lys)

dbSNP: rs1554700678

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000522148	SCV000621333	pathogenic	not provided	2023-09-08	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 36130591, 33874999)
The Genetics Institute, Rambam Health Care Campus	RCV000627090	SCV000747834	likely pathogenic	Au-Kline syndrome	2018-04-01	criteria provided, single submitter	clinical testing	This sequence change replaces Glutamic acid with Lysine at codon 85 of the HNRNPK protein p.(Glu85Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (gmomAD, dbSNP,). This variant was found in an individual with clinical symptomes compatible with Au-Kline syndrome (MIM:616580 ), de novo inheritance was confirmed. ClinVar contains an entry for this variant (Variation ID: 452520). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55").
Ambry Genetics	RCV001267488	SCV001445669	uncertain significance	Inborn genetic diseases	2018-03-01	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000522148	SCV001447542	likely pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
3billion	RCV000627090	SCV002572966	uncertain significance	Au-Kline syndrome	2022-09-01	criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.29; 3Cnet: 0.98). Same nucleotide change resulting in same amino acid change has been previously reported as likely pathogenic and uncertain significance for HNRNPK -related disorder (ClinVar ID: VCV000452520). Threrefore, the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline.
MGZ Medical Genetics Center	RCV000627090	SCV002578985	likely pathogenic	Au-Kline syndrome	2021-12-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000522148	SCV004042360	likely pathogenic	not provided	2023-09-01	criteria provided, single submitter	clinical testing	HNRNPK: PS2, PM2, PS4:Moderate, PP2
OMIM	RCV000627090	SCV002605170	pathogenic	Au-Kline syndrome	2022-11-18	no assertion criteria provided	literature only