ClinVar Miner

Submissions for variant NM_030787.4(CFHR5):c.486dup (p.Glu163fs) (rs565457964)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000455834 SCV000538667 uncertain significance not specified 2017-10-18 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Glu163ArgfsX3 5 variant in CFHR5 (also reported as p.Glu163Arg and p.Asn197Stop) has been prev iously reported in at least two heterozygous individuals with CFHR5-deficiency a nd complement-mediated kidney diseases, as well as at least three asymptomatic i ndividuals (1 control and 2 family members of 1 of the heterozygotes; Monteferra nte 2007, Vernon 2012, and Figueres 2014). This variant has also been reported i n ClinVar (Variation ID#402534). It has been identified in 0.31% (395/126014) Eu ropean chromosomes by the Genome Aggregation Database (http://gnomad.broadinstit ute.org; rs565457964). This variant is predicted to cause a frameshift, which al ters the protein?s amino acid sequence beginning at position 163 and leads to a premature termination codon 35 amino acids downstream. This alteration is then p redicted to lead to a truncated or absent protein. In summary, while the clinica l significance of the p.Glu163ArgfsX35 variant is uncertain, these data suggest that it is more likely to be benign.
GeneDx RCV000767072 SCV000568842 uncertain significance not provided 2017-12-29 criteria provided, single submitter clinical testing The c.486dupA variant in the CFHR5 gene has previously been reported (as c.485dupA and Asn1975Stop due to alternative nomenclature) in association with renal disease, but it has also been reported in clinically asymptomatic individuals (Monteferrante et al., 2007; Vernon et al., 2012; Figueres et al., 2014). The c.486dupA variant causes a frameshift starting with codon Glutamic Acid 163, changes this amino acid to an Arginine residue, and creates a premature Stop codon at position 35 of the new reading frame, denoted p.Glu163ArgfsX35. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. However, the c.486dupA variant is observed in 564/276,160 (0.20%) alleles in large population cohorts (Lek et al., 2016). We interpret c.486dupA as a variant of uncertain significance.
Invitae RCV000767072 SCV001028978 likely benign not provided 2019-12-31 criteria provided, single submitter clinical testing
Mendelics RCV000030802 SCV001135489 benign CFHR5 deficiency 2019-05-28 criteria provided, single submitter clinical testing
Cavalleri Lab, Royal College of Surgeons in Ireland RCV001171343 SCV001328290 uncertain significance Chronic kidney disease 2020-05-28 criteria provided, single submitter research PVS1, BS1
OMIM RCV000030802 SCV000053471 pathogenic CFHR5 deficiency 2012-07-01 no assertion criteria provided literature only

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