ClinVar Miner

Submissions for variant NM_000174.4(GP9):c.182A>G (p.Asn61Ser) (rs5030764)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000275909 SCV000440790 pathogenic Bernard Soulier syndrome 2017-08-28 criteria provided, single submitter clinical testing The GP9 c.182A>G (p.Asn61Ser) missense variant has been reported in four studies in which it is found in a total of ten individuals with bleeding abnormalities characteristic of Bernard-Soulier syndrome, including in six in a homozygous state and in four (including three siblings) in a compound heterozygous state (Wright et al. 1993; Clemetson et al. 1994; Sachs et al. 2003; Bragadottir et al. 2015). The variant was also found in a heterozygous state in six unaffected family members. The p.Asn61Ser variant was absent from 208 control alleles and is reported at a frequency of 0.001073 in the non-Finnish European population of the Exome Aggregation Consortium. Based on the evidence, the p.Asn61Ser variant is classified as pathogenic for Bernard-Soulier syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Fulgent Genetics,Fulgent Genetics RCV000275909 SCV000893631 likely pathogenic Bernard Soulier syndrome 2018-10-31 criteria provided, single submitter clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge RCV000275909 SCV000899314 pathogenic Bernard Soulier syndrome 2019-02-01 criteria provided, single submitter research
NIHR Bioresource Rare Diseases, University of Cambridge RCV000851932 SCV000899315 likely pathogenic Thrombocytopenia 2019-02-01 criteria provided, single submitter research
NIHR Bioresource Rare Diseases, University of Cambridge RCV000761618 SCV000899316 pathogenic Macrothrombocytopenia 2019-02-01 criteria provided, single submitter research
Invitae RCV001062554 SCV001227361 pathogenic not provided 2020-10-28 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 61 of the GP9 protein (p.Asn61Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs5030764, ExAC 0.1%). This variant has been observed to segregate with Bernard-Soulier syndrome in several individuals and families (PMID: 8481514, 28765788, 25370924, 14510954, 28131619). This variant is also known as Asn45Ser in the literature. ClinVar contains an entry for this variant (Variation ID: 13529). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001062554 SCV001250029 pathogenic not provided 2019-07-01 criteria provided, single submitter clinical testing
OMIM RCV000014484 SCV000034735 pathogenic Bernard-Soulier syndrome type C 2003-10-01 no assertion criteria provided literature only
Division of Human Genetics,Children's Hospital of Philadelphia RCV000275909 SCV000536920 likely pathogenic Bernard Soulier syndrome 2016-02-21 no assertion criteria provided research
GenomeConnect, ClinGen RCV000275909 SCV000784694 not provided Bernard Soulier syndrome no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000761618 SCV000891711 pathogenic Macrothrombocytopenia 2019-03-22 no assertion criteria provided clinical testing

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