Submissions for variant NM_021008.4(DEAF1):c.926del (p.Leu309fs)

dbSNP: rs1417226023

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002222872	SCV002500104	likely pathogenic	Intellectual disability, autosomal dominant 24	2022-03-04	criteria provided, single submitter	clinical testing	Variant summary: DEAF1 c.926delT (p.Leu309ArgfsX6) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4e-06 in 251490 control chromosomes (gnomAD). To our knowledge, no occurrence of c.926delT in individuals affected with Mental Retardation, Autosomal Dominant 24 and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003089145	SCV003021741	pathogenic	not provided	2023-09-30	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu309Argfs*6) in the DEAF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DEAF1 are known to be pathogenic (PMID: 30923367). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with DEAF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1677014). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences	RCV004529102	SCV004112774	likely pathogenic	DEAF1-related disorder	2023-03-23	criteria provided, single submitter	clinical testing	The DEAF1 c.926delT variant is predicted to result in a frameshift and premature protein termination (p.Leu309Argfs*6). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-681033-CA-C). Frameshift variants in DEAF1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.