ClinVar Miner

Submissions for variant NM_000518.4(HBB):c.208G>A (p.Gly70Ser) (rs33947415)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Bodamer Research Lab,Boston Children's Hospital RCV000396079 SCV000599992 uncertain significance beta Thalassemia 2016-02-24 no assertion criteria provided clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000587680 SCV000333005 likely pathogenic not provided 2015-08-08 criteria provided, single submitter clinical testing
GenomeConnect, ClinGen RCV000709890 SCV000840231 not provided Beta-thalassemia, dominant inclusion body type; Fetal hemoglobin quantitative trait locus 1; Hb SS disease; beta Thalassemia 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.
Integrated Genetics/Laboratory Corporation of America RCV000029969 SCV000052624 uncertain significance Beta thalassemia intermedia 2015-10-02 no assertion criteria provided clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587680 SCV000697092 uncertain significance not provided 2017-04-12 criteria provided, single submitter clinical testing Variant summary: The HBB c.208G>A (p.Gly70Ser) variant involves the alteration of a non-conserved nucleotide and is predicted to be benign by 3/4 in silico tools (SNPs&GO not captured due to low reliability index). This variant was found in 102/121396 control chromosomes from ExAC at a frequency of 0.0008402, which does not exceed the estimated maximal expected allele frequency of a pathogenic HBB variant (0.0111803). In families carrying this variant (aka Hb City of Hope or Hb CH) heterozygous carriers (at least nine from six families) were found to be clinically and hematologically unaffected. However, three studies show that Gly69Ser mutation should not be considered as a clinically/functionally silent in compound heterozygosity with any other known abnormal globin hemoglobin gene (Kultar et al., 1989; Paradise et al., 2010; Vinciguerra et al., 2015). Two probands who had this variant in compound heterozygosity with another beta-0-thal mutation presented with mild to moderate phenotype (moderate microcytic, hypochromic anemia, jaundice) with potential need for transfusions, from occasional to regular, whereas one proband who had this variant in compound heterozygous state with HbS (ie p.E7V), presented with severe anemic phenotype complicated with a fatal parvovirus B19 chronic infection. Although multiple clinical diagnostic laboratories/reputable databases have classified this variant as VUS, one lab has classified it as likely pathogenic. Taken together, this variant is classified as VUS-possibly pathogenic until more information becomes available.
OMIM RCV000016301 SCV000036569 other HEMOGLOBIN CITY OF HOPE 2017-12-12 no assertion criteria provided literature only

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