Submissions for variant NM_001283009.2(RTEL1):c.2274G>A (p.Ala758=)

gnomAD frequency: 0.79477  dbSNP: rs2236506

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000455713	SCV000540227	benign	not specified	2018-03-06	criteria provided, single submitter	clinical testing	The A "variant" is the major allele in the Genome Aggregation Database (gnomAD; http://gnomad.broadinstitute.org; dbSNP rs2236506).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587848	SCV000699746	benign	not provided	2017-07-10	criteria provided, single submitter	clinical testing	Variant summary: The RTEL1 c.2346G>A (p.Ala782Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a benign outcome for this variant. 5/5 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 88140/118930 control chromosomes (33801 homozygotes) at a frequency of 0.7411082, which is approximately 663 times the estimated maximal expected allele frequency of a pathogenic RTEL1 variant (0.001118), indicating the variant is the major allele and is benign. In addition, one clinical diagnostic laboratory classified this variant as benign. Taken together, this variant is classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001519413	SCV001728279	benign	Dyskeratosis congenita, autosomal recessive 5; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001543249	SCV001761776	benign	Dyskeratosis congenita, autosomal recessive 5	2021-07-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001543250	SCV001761777	benign	Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3	2021-07-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000587848	SCV001913634	benign	not provided	2018-11-28	criteria provided, single submitter	clinical testing
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	RCV000455713	SCV004232949	benign	not specified	2024-01-24	criteria provided, single submitter	clinical testing	This variant is classified as Benign based on local population frequency. This variant was detected in 89% of patients studied by a panel of primary immunodeficiencies. Number of patients: 85. Only high quality variants are reported.
Breakthrough Genomics, Breakthrough Genomics	RCV000587848	SCV005314078	benign	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV001272651	SCV001454890	benign	Dyskeratosis congenita	2020-09-16	no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000455713	SCV001957010	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000455713	SCV001963992	benign	not specified		no assertion criteria provided	clinical testing
GenomeConnect, ClinGen	RCV000587848	SCV002074741	not provided	not provided		no assertion provided	phenotyping only	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing.