Submissions for variant NM_004260.4(RECQL4):c.215C>T (p.Ala72Val)

gnomAD frequency: 0.00005  dbSNP: rs763453097

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000470370	SCV000545945	uncertain significance	Baller-Gerold syndrome	2024-10-21	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 72 of the RECQL4 protein (p.Ala72Val). This variant is present in population databases (rs763453097, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. ClinVar contains an entry for this variant (Variation ID: 406973). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV001543123	SCV001761640	uncertain significance	Rothmund-Thomson syndrome type 2	2021-06-24	criteria provided, single submitter	clinical testing	The RECQL4 c.215C>T (p.Ala72Val) missense change is present at a maximum subpopulation frequency of 0.039% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/8-145742573-G-A). In silico tools predict a benign effect of this variant on protein function (BP4), but to our knowledge these predictions have not been confirmed by functional assays. To our knowledge, this variant has not been reported in individuals with RECQL4-associated disorders. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: BP4.
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University	RCV003153603	SCV003843336	benign	Ovarian cancer	2022-01-01	criteria provided, single submitter	clinical testing
GeneDx	RCV004794389	SCV005415383	uncertain significance	not provided	2024-05-24	criteria provided, single submitter	clinical testing	In silico analysis indicates that this missense variant does not alter protein structure/function; Observed in an individual with colorectal cancer (PMID: 31360874); This variant is associated with the following publications: (PMID: 29641532, 31360874)