Submissions for variant NM_014915.3(ANKRD26):c.4445T>C (p.Ile1482Thr)

gnomAD frequency: 0.00437  dbSNP: rs80097260

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000497483	SCV000590347	likely benign	not provided	2021-09-13	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000497483	SCV001118771	benign	not provided	2025-01-27	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001102741	SCV001259428	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.
Genome-Nilou Lab	RCV001102741	SCV002539473	benign	Thrombocytopenia 2	2021-12-05	criteria provided, single submitter	clinical testing
Genetics and Molecular Pathology, SA Pathology	RCV001102741	SCV002761647	benign	Thrombocytopenia 2	2019-10-10	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000497483	SCV005227636	likely benign	not provided		criteria provided, single submitter	not provided
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001102741	SCV005876243	likely benign	Thrombocytopenia 2	2024-01-24	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000497483	SCV001550043	likely benign	not provided		no assertion criteria provided	clinical testing	The ANKRD26 p.Ile1482Thr variant was not identified in the literature but was identified in dbSNP (ID: rs80097260), ClinVar (classified as uncertain significance by GeneDx) and LOVD 3.0 (classified as likely benign). The variant was identified in control databases in 1222 of 280530 chromosomes (3 homozygous) at a frequency of 0.004356 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (Finnish) in 224 of 24996 chromosomes (freq: 0.008961), European (non-Finnish) in 830 of 128428 chromosomes (freq: 0.006463), Other in 33 of 7132 chromosomes (freq: 0.004627), Latino in 99 of 35336 chromosomes (freq: 0.002802), African in 29 of 24190 chromosomes (freq: 0.001199), South Asian in 5 of 30586 chromosomes (freq: 0.000164), Ashkenazi Jewish in 1 of 10356 chromosomes (freq: 0.000097), and East Asian in 1 of 19506 chromosomes (freq: 0.000051). The p.Ile1482 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000497483	SCV001800522	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000497483	SCV001967504	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003915355	SCV004731634	benign	ANKRD26-related disorder	2020-09-23	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).