ClinVar Miner

Submissions for variant NM_006420.3(ARFGEF2):c.625G>A (p.Glu209Lys) (rs28937880)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center RCV000005353 SCV000267212 uncertain significance Heterotopia, periventricular, autosomal recessive 2016-03-18 criteria provided, single submitter reference population
GeneDx RCV000425899 SCV000521221 uncertain significance not specified 2017-01-19 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ARFGEF2 gene. The E209K variant has been reported previously as a homozygous variant in two siblings with autosomal recessive periventricular heterotopia with microcephaly (ARPHM) (Sheen et al., 2004). The E209K variant is observed in 140/11,574 (1.2%) alleles from individuals of Latino background in large population cohorts, which is greater than expected for this disorder (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The E209K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Athena Diagnostics Inc RCV000710616 SCV000840859 uncertain significance not provided 2017-12-05 criteria provided, single submitter clinical testing
Invitae RCV000710616 SCV001014932 benign not provided 2019-12-31 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000005353 SCV001159585 uncertain significance Heterotopia, periventricular, autosomal recessive 2019-06-26 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000005353 SCV001302284 benign Heterotopia, periventricular, autosomal recessive 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Broad Institute Rare Disease Group, Broad Institute RCV000005353 SCV001435235 benign Heterotopia, periventricular, autosomal recessive criteria provided, single submitter research The homozygous p.Glu209Lys variant in ARFGEF has been identified in at least 1 Turkish individual with consanguineous parents and periventricular heterotopia with microcephaly (PMID: 14647276, 28333917). This variant has also been identified in >1% of Latino chromosomes and 1 homozygote by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for autosomal recessive periventricular heterotopia with microcephaly.
OMIM RCV000005353 SCV000025531 uncertain significance Heterotopia, periventricular, autosomal recessive 2004-01-01 no assertion criteria provided literature only

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