Submissions for variant NM_004985.5(KRAS):c.264A>G (p.Lys88=)

gnomAD frequency: 0.00021  dbSNP: rs370920665

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000213935	SCV000270323	likely benign	not specified	2015-10-13	criteria provided, single submitter	clinical testing	p.Lys88Lys in Exon 03 of KRAS: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence. It has been identified in 8/16432 South Asian ch romosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute. org).
Illumina Laboratory Services, Illumina	RCV000369643	SCV000377751	uncertain significance	Noonan syndrome	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000586846	SCV000513423	benign	not provided	2018-05-21	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586846	SCV000699771	benign	not provided	2017-08-10	criteria provided, single submitter	clinical testing	Variant summary: The KRAS c.264A>G (p.Lys88Lys) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change, located in the P-loop containing nucleoside triphosphate hydrolase domain (IPR027417) (InterPro). One in silico tool predicts a damaging outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in the large control database ExAC in 21/120432 control chromosomes at a frequency of 0.0001744, which is approximately 14 times the estimated maximal expected allele frequency of a pathogenic KRAS variant (0.0000125), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. The variant of interest has not, to our knowledge, been reported as a germline variant in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Eurofins Ntd Llc (ga)	RCV000213935	SCV000707276	likely benign	not specified	2017-03-24	criteria provided, single submitter	clinical testing
Invitae	RCV001512187	SCV001719552	benign	RASopathy	2022-10-18	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003947702	SCV004763834	likely benign	KRAS-related condition	2020-08-24	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).