Submissions for variant NM_001365951.3(KIF1B):c.2115+6956A>G

gnomAD frequency: 0.00525  dbSNP: rs148481786

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000281337	SCV000335078	benign	not specified	2015-09-28	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000423645	SCV000511663	likely benign	not provided	2017-01-04	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000423645	SCV001472878	benign	not provided	2023-11-22	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000423645	SCV004042414	benign	not provided	2024-05-01	criteria provided, single submitter	clinical testing	KIF1B: PP2, BP4, BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV003920059	SCV004735870	benign	KIF1B-related disorder	2019-04-17	criteria provided, single submitter	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).
Center of Medical Genetics and Primary Health Care	RCV001270154	SCV001450447	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000423645	SCV001550051	likely benign	not provided		no assertion criteria provided	clinical testing	The KIF1B p.Glu1006Gly variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs148481786) and ClinVar (classified as benign by EGL Genetics and likely benign by Children's Mercy Hospital) The variant was identified in control databases in 1644 of 282350 chromosomes (14 homozygous) at a frequency of 0.005823 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: Ashkenazi Jewish in 290 of 10356 chromosomes (freq: 0.028), European (Finnish) in 249 of 25120 chromosomes (freq: 0.009912), Other in 67 of 7192 chromosomes (freq: 0.009316), European (non-Finnish) in 859 of 128920 chromosomes (freq: 0.006663), Latino in 89 of 35424 chromosomes (freq: 0.002512), South Asian in 71 of 30614 chromosomes (freq: 0.002319) and African in 19 of 24776 chromosomes (freq: 0.000767), while the variant was not observed in the East Asian population. 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.Glu1006 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. 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.
Clinical Genetics, Academic Medical Center	RCV000281337	SCV001925285	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000423645	SCV001929787	likely benign	not provided		no assertion criteria provided	clinical testing