Submissions for variant NM_004333.6(BRAF):c.2128-5dup

dbSNP: rs373442098

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000037942	SCV000226781	benign	not specified	2014-09-05	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000196864	SCV000252786	benign	RASopathy	2025-02-04	criteria provided, single submitter	clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000037942	SCV000257952	benign	not specified	2015-06-26	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000269428	SCV000466953	uncertain significance	Noonan syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000324595	SCV000466954	uncertain significance	Cardio-facio-cutaneous syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000379190	SCV000466955	uncertain significance	Noonan syndrome with multiple lentigines	2016-06-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000037942	SCV001361992	benign	not specified	2019-10-10	criteria provided, single submitter	clinical testing	Variant summary: BRAF c.2128-5dupT alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 151920 control chromosomes. However, multiple benign variants have been found in this polyT region. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (2x benign, 1x VUS). Based on the evidence outlined above, the variant was classified as benign.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813336	SCV002060468	benign	Noonan syndrome and Noonan-related syndrome	2021-07-08	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037942	SCV000061607	not provided	not specified	2014-03-13	no assertion provided	clinical testing	2128-5_2128-4insT in intron 17 of BRAF: This variant is not expected to have clinical significance because it shifts but does not alter the splice consensus sequence.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001573246	SCV001798813	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000037942	SCV001925149	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001573246	SCV001973114	likely benign	not provided		no assertion criteria provided	clinical testing
Genetics and Genomics Program, Sidra Medicine	RCV004732585	SCV005367910	uncertain significance	Congenital long QT syndrome		no assertion criteria provided	research	The c.2128-5dupT variant in BRAF affects the splice region and is not reported in population databases like gnomAD, indicating rarity. However, there is currently insufficient evidence regarding its impact on splicing or its clinical significance. Due to the lack of supporting data, this variant is classified as a VUS.