Submissions for variant NM_014915.3(ANKRD26):c.-127A>T

dbSNP: rs1589393799

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000851621	SCV000899389	likely pathogenic	Thrombocytopenia	2019-02-01	criteria provided, single submitter	research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001615051	SCV002548509	pathogenic	Thrombocytopenia 2	2022-05-25	criteria provided, single submitter	clinical testing	Variant summary: ANKRD26 c.-127A>T alters a non-conserved nucleotide located in the untranslated mRNA region upstream of the initiation codon. Mutations in the 5'-UTR of the ANKRD26 gene have been reported as a frequent cause of Thrombocytopenia 2 (example, Bluteau_2014). The variant was absent in 31404 control chromosomes. c.-127A>T has been reported in the literature in multiple individuals affected with Thrombocytopenia 2 (example, Pippucci_2011, Zidan_2021). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function and demonstrated that this and other 5'-UTR variants in ANKRD26 gene led to loss of inhibitory regulatory function of RUNX1 and FLH1 in a luciferase based assay in K562 cells in vitro (example, Bluteau_2014). One submitter has provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002533969	SCV003441422	pathogenic	not provided	2023-02-18	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 not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with thrombocytopenia (PMID: 21211618, 25902755, 32659145). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 626943). Studies have shown that this variant alters ANKRD26 gene expression (PMID: 21211618). For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Laboratories, Mayo Clinic	RCV002533969	SCV005413934	pathogenic	not provided	2024-07-23	criteria provided, single submitter	clinical testing	PM1, PM2, PS3, PS4_moderate
OMIM	RCV001615051	SCV000045130	pathogenic	Thrombocytopenia 2	2011-01-07	no assertion criteria provided	literature only
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV001615051	SCV004041747	pathogenic	Thrombocytopenia 2	2023-10-09	no assertion criteria provided	clinical testing