Submissions for variant NM_001017995.3(SH3PXD2B):c.2227G>A (p.Val743Met)

gnomAD frequency: 0.00074  dbSNP: rs141103005

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000330657	SCV000456317	likely benign	Frank-Ter Haar syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000899923	SCV001044214	likely benign	not provided	2025-01-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003317197	SCV004020759	likely benign	not specified	2023-06-13	criteria provided, single submitter	clinical testing	Variant summary: SH3PXD2B c.2227G>A (p.Val743Met) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0013 in 250864 control chromosomes in the gnomAD database, including 1 homozygote, suggesting the variant is likely a benign polymorphism. To our knowledge, no occurrence of c.2227G>A in individuals affected with Frank-Ter Haar Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and both classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
CeGaT Center for Human Genetics Tuebingen	RCV000899923	SCV004158031	likely benign	not provided	2024-10-01	criteria provided, single submitter	clinical testing	SH3PXD2B: BP4
Breakthrough Genomics, Breakthrough Genomics	RCV000899923	SCV005221994	likely benign	not provided		criteria provided, single submitter	not provided
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000899923	SCV001799984	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000899923	SCV001969690	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003902366	SCV004723843	likely benign	SH3PXD2B-related disorder	2023-04-13	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).