ClinVar Miner

Submissions for variant NM_001015877.2(PHF6):c.820C>T (p.Arg274Ter)

dbSNP: rs1556019107
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics, Fulgent Genetics RCV002531897 SCV005683324 pathogenic Borjeson-Forssman-Lehmann syndrome 2024-04-05 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002531897 SCV003445904 pathogenic Borjeson-Forssman-Lehmann syndrome 2022-07-11 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 521446). This premature translational stop signal has been observed in individual(s) with clinical features of PHF6-related conditions (PMID: 28539120). This sequence change creates a premature translational stop signal (p.Arg274*) in the PHF6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PHF6 are known to be pathogenic (PMID: 12415272, 24092917, 25099957, 26648834).
GeneDx RCV001092161 SCV002817800 pathogenic not provided 2022-06-28 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32552793, 28539120, 35662002)
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV002252179 SCV002522725 pathogenic See cases 2021-05-20 criteria provided, single submitter clinical testing ACMG classification criteria: PVS1, PS4, PM2
CeGaT Center for Human Genetics Tuebingen RCV001092161 SCV001248542 pathogenic not provided 2018-12-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000624597 SCV000742039 pathogenic Inborn genetic diseases 2025-04-28 criteria provided, single submitter clinical testing The c.820C>T (p.R274*) alteration, located in exon 8 (coding exon 7) of the PHF6 gene, consists of a C to T substitution at nucleotide position 820. This changes the amino acid from a arginine (R) to a stop codon at amino acid position 274. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant was determined to be de novo in at least one individual with features consistent with Borjeson-Forssman-Lehmann syndrome (Zahir, 2017; Gerber, 2022). Based on the available evidence, this alteration is classified as pathogenic.

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