Submissions for variant NM_014915.3(ANKRD26):c.-113A>C

gnomAD frequency: 0.00038  dbSNP: rs886046949

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000317917	SCV000362087	uncertain significance	Thrombocytopenia	2016-06-14	criteria provided, single submitter	clinical testing	Noris et al. (2001) identified the c.-113A>C variant in the 5' untranslated region of the ANKRD26 gene in an Italian patient with thrombocytopenia 2. Available relatives of this patient were tested and the variant was detected in two other affected individuals. Control data are unavailable for this variant which it is not found in the 1000 Genomes Project, the Exome Sequencing Project, or the Exome Aggregation Consortium. The evidence for this variant is limited. The c.-113A>C variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for thrombocytopenia.
GeneDx	RCV001571174	SCV001795595	uncertain significance	not provided	2024-06-27	criteria provided, single submitter	clinical testing	Observed in individuals with thrombocytopenia but also in unaffected controls (PMID: 21467542, 28669401); Nucleotide is not conserved across species and the substitution has no predicted effect on splicing; This variant is associated with the following publications: (PMID: 28277066, 24430186, 21467542, 32351539, 31275945, 28669401, 35751752, Kuzmanovic2022[abstract], 35587581)
Genetic Services Laboratory, University of Chicago	RCV001820874	SCV002068943	uncertain significance	not specified	2020-07-15	criteria provided, single submitter	clinical testing	DNA sequence analysis of the ANKRD26 gene demonstrated a sequence change in the 5 prime untranslated region (5'UTR), c.-113A>C. This sequence change has been described in the gnomAD database with a low population frequency of 0.019% (dbSNP rs886046949). The c.-113A>C change has been described in a patient with thrombocytopenia (PMID: 21467542). This sequence change occurs in a region where other pathogenic sequence changes have been reported in patients with ANKRD26-related thrombocytopenia. The functional significance of this sequence change is not known at present and its contribution to a disease phenotype cannot definitively be determined.
Mendelics	RCV001820874	SCV002516866	uncertain significance	not specified	2022-05-04	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001571174	SCV003441612	uncertain significance	not provided	2024-01-16	criteria provided, single submitter	clinical testing	This variant occurs in a non-coding region of the ANKRD26 gene. It does not change the encoded amino acid sequence of the ANKRD26 protein. This variant is present in population databases (no rsID available, gnomAD 0.03%). This variant has been observed in individual(s) with thrombocytopenia 2 (PMID: 21467542). It has also been observed to segregate with disease in related individuals. This variant has been observed to be homozygous or hemizygous in an individual who did not have the expected clinical features for that genetic result (PMID: 28669401). ClinVar contains an entry for this variant (Variation ID: 299768). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
PreventionGenetics, part of Exact Sciences	RCV003920234	SCV004734256	uncertain significance	ANKRD26-related disorder	2024-08-09	no assertion criteria provided	clinical testing	The ANKRD26 c.-113A>C variant is located in the 5' untranslated region. This variant has been reported in three individuals from the same family with thrombocytopenia (Noris et al. 2011. PubMed ID: 21467542). This variant has also been reported in a large screen of individuals with rare diseases that found the variant in multiple individuals who did not display bleeding/platelet phenotypes (Greene et al. 2017. PubMed ID: 28669401). This variant is reported in 0.032% of alleles in individuals of European (Non-Finnish) descent in gnomAD, which may be too frequent to be a fully-penetrant pathogenic variant. This variant is interpreted as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/299768/). At this time, the clinical significance of this variant is uncertain due to the conflicting evidence.