Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_004287.5(GOSR2):c.200G>A(p.Arg67Lys) variant causes a missense change. The variant allele was found at a frequency of 0.343 in 1,435,212 control chromosomes in the GnomAD database, including 85,927 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R67Q) has been classified as Uncertain significance.
GOSR2 (HGNC:4431): (golgi SNAP receptor complex member 2) This gene encodes a trafficking membrane protein which transports proteins among the medial- and trans-Golgi compartments. Due to its chromosomal location and trafficking function, this gene may be involved in familial essential hypertension. [provided by RefSeq, Mar 2016]
BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (MetaRNN=0.0017098784).
BP6
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BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-46931204-G-A is Benign according to our data. Variant chr17-46931204-G-A is described in ClinVar as [Benign]. Clinvar id is 129165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-46931204-G-A is described in Lovd as [Benign].
BA1
?
BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.
Genetic Services Laboratory, University of Chicago
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Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, no assertion criteria provided
clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht
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Benign, criteria provided, single submitter
clinical testing
PreventionGenetics, part of Exact Sciences
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Benign, no assertion criteria provided
clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
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Benign, criteria provided, single submitter
clinical testing
Eurofins Ntd Llc (ga)
Jul 09, 2014
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Benign, no assertion criteria provided
clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
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not provided Benign:2
Benign, criteria provided, single submitter
clinical testing
Athena Diagnostics
Apr 20, 2017
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Benign, criteria provided, single submitter
clinical testing
GeneDx
Mar 03, 2015
This variant is associated with the following publications: (PMID: 19057520) -
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -