Submissions for variant NM_014915.3(ANKRD26):c.4636G>C (p.Asp1546His)

gnomAD frequency: 0.00006  dbSNP: rs753924410

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000501275	SCV000593198	uncertain significance	not specified	2016-09-13	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001107979	SCV001265169	benign	Thrombocytopenia 2	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Baylor Genetics	RCV001107979	SCV001524164	uncertain significance	Thrombocytopenia 2	2019-09-26	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp	RCV001249337	SCV003483433	uncertain significance	not provided	2024-07-15	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 1546 of the ANKRD26 protein (p.Asp1546His). This variant is present in population databases (rs753924410, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with ANKRD26-related conditions. ClinVar contains an entry for this variant (Variation ID: 434206). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx	RCV001249337	SCV003918533	uncertain significance	not provided	2022-10-11	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV004023359	SCV004903010	uncertain significance	Inborn genetic diseases	2024-10-04	criteria provided, single submitter	clinical testing	The p.D1546H variant (also known as c.4636G>C), located in coding exon 31 of the ANKRD26 gene, results from a G to C substitution at nucleotide position 4636. The aspartic acid at codon 1546 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
GenomeConnect, ClinGen	RCV001249337	SCV001423306	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as Uncertain significance and reported on 11-06-2016 by Lab or GTR ID 1238. 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.