Submissions for variant NM_001365951.3(KIF1B):c.2115+6360G>T

gnomAD frequency: 0.01961  dbSNP: rs41274458

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000202848	SCV000258273	benign	not specified	2015-02-13	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001357609	SCV001159541	benign	not provided	2023-11-22	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001357609	SCV001553125	likely benign	not provided		no assertion criteria provided	clinical testing	The KIF1B p.Met807Ile variant was identified in dbSNP (ID: rs41274458) and ClinVar (classified as benign by the Division of Genomic Diagnostics, The Children's Hospital of Philadelphia) but was not identified in Cosmic or LOVD 3.0. The variant was also identified in control databases in 5217 of 282018 chromosomes (87 homozygous) at a frequency of 0.018499 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (Finnish) in 1052 of 25118 chromosomes (freq: 0.04188), European (non-Finnish) in 3406 of 128482 chromosomes (freq: 0.02651), Other in 153 of 7206 chromosomes (freq: 0.02123), Latino in 346 of 35412 chromosomes (freq: 0.009771), Ashkenazi Jewish in 70 of 10320 chromosomes (freq: 0.006783), African in 102 of 24938 chromosomes (freq: 0.00409), South Asian in 87 of 30608 chromosomes (freq: 0.002842) and East Asian in 1 of 19934 chromosomes (freq: 0.00005). This variant was previously reported somatically in neuroblastoma tumors (Chen_2014_PMID: 24469107). 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. The p.Met807 residue is not conserved in mammals and 5 of 5 computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein. 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)	RCV001357609	SCV001798697	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000202848	SCV001919203	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001357609	SCV001929450	likely benign	not provided		no assertion criteria provided	clinical testing