ClinVar Miner

Submissions for variant NM_005142.3(CBLIF):c.183_186del (p.Met61fs)

dbSNP: rs765896727
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000686858 SCV000814395 pathogenic Hereditary intrinsic factor deficiency 2024-01-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Met61Ilefs*8) in the GIF gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GIF are known to be pathogenic (PMID: 14576042, 22929189). This variant is present in population databases (rs765896727, gnomAD 0.06%). This premature translational stop signal has been observed in individuals with intrinsic factor deficiency (PMID: 14576042, 19036097, 22854512, 22929189). ClinVar contains an entry for this variant (Variation ID: 566919). For these reasons, this variant has been classified as Pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756202 SCV000883938 pathogenic not provided 2017-09-08 criteria provided, single submitter clinical testing The c.183_186delGAAT; p.Met61fs was found homozygote in an 11 year old African American female with megaloblastic anemia and cobalamin deficiency, who inherited the variant from a heterozygote mother (Yassin, 2004). This variant was further observed in three patients of African descent, who were diagnosed with juvenile cobalamin deficiency, whereby parental haplotype analysis indicated a likely founder event of the deletion in the Sub-Saharan West-African lineage (Ament, 2009). Consistent with this study, the c.183_186delGAAT variant is identified on 17 out of 276,970 chromosomes, 14 from the African population, with an overall frequency of 0.006 percent listed in the Genome Aggregation Database (gnomAD). This variant is also reported to the ClinVar database with a pathogenic classification (Variation ID: 1743). Altogether the c.183_186delGAAT is pathogenic.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV000686858 SCV003807841 pathogenic Hereditary intrinsic factor deficiency 2023-04-05 criteria provided, single submitter clinical testing ACMG classification criteria: PVS1 very strong, PM2 supporting, PM3 moderated, PP4
OMIM RCV000686858 SCV000021969 pathogenic Hereditary intrinsic factor deficiency 2005-03-15 no assertion criteria provided literature only

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