Submissions for variant NM_004985.5(KRAS):c.178_198dup (p.Ala66_Met67insGlyGlnGluGluTyrSerAla)

dbSNP: rs2548920482

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Clinical Genomics Laboratory, Washington University in St. Louis	RCV003458962	SCV004176930	likely pathogenic	Vascular malformation	2023-08-06	criteria provided, single submitter	clinical testing	The KRAS c.178_198dup (p.Gly60_Ala66dup) was identified at an allelic fraction consistent with somatic origin. This variant, to our knowledge, has not been reported in vascular anomalies, but has been reported in a child with atypical myeloproliferative neoplasm (White Y et al., PMID: 26854029). However, many other in-frame indels in this region have been identified in individuals with disorders of somatic mosaicism (Hou et al., PMID: 36571464). This variant is absent from the general population (gnomAD v.2.1), indicating it is not a common variant and resides within a region, the switch II domain, amino acids 58-72, of KRAS that is defined as a critical functional domain (Eijkelenboom A et al., PMID: 31160609; Hou et al., PMID: 36571464). The KRAS c.178_198dup (p.Gly60_Ala66dup) variant is predicted to cause a change in the length of the protein due to an in-frame duplication of seven amino acid(s) in a non-repeat region. Based on an internally-developed protocol informed by the ACMG/AMP guidelines (Richards S et al., PMID: 25741868) and gene-specific practices from the ClinGen Criteria Specification Registry, the KRAS c.178_198dup (p.Gly60_Ala66dup) variant is classified as likely pathogenic.