{"entity": "researcher", "timestamp": "2026-08-20T20:47:31.315Z", "family": "Gudmundsson", "given": "Sanna", "initials": "S", "orcid": "0000-0002-2332-074X", "affiliations": ["Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. sgudmund@broadinstitute.org.", "Center for Genomic Medicine & Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. sgudmund@broadinstitute.org.", "Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. sgudmund@broadinstitute.org.", "Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden. sgudmund@broadinstitute.org."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/167f305a31a3449c82851b262d13ee87.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/167f305a31a3449c82851b262d13ee87"}}, "publications": [{"entity": "publication", "iuid": "75adad45b2814bf2abe2851ab5191460", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/75adad45b2814bf2abe2851ab5191460.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/75adad45b2814bf2abe2851ab5191460"}}, "title": "Exploring penetrance of clinically relevant variants in over 800,000 humans from the Genome Aggregation Database.", "authors": [{"family": "Gudmundsson", "given": "Sanna", "initials": "S", "orcid": "0000-0002-2332-074X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/167f305a31a3449c82851b262d13ee87.json"}}, {"family": "Singer-Berk", "given": "Moriel", "initials": "M"}, {"family": "Stenton", "given": "Sarah L", "initials": "SL", "orcid": "0000-0003-4071-449X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f2f589a32dff4f73a37e6bde28a148fa.json"}}, {"family": "Goodrich", "given": "Julia K", "initials": "JK"}, {"family": "Wilson", "given": "Michael W", "initials": "MW"}, {"family": "Einson", "given": "Jonah", "initials": "J"}, {"family": "Watts", "given": "Nicholas A", "initials": "NA"}, {"family": "Genome Aggregation Database Consortium", "given": "", "initials": ""}, {"family": "Lappalainen", "given": "Tuuli", "initials": "T", "orcid": "0000-0002-7746-8109", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e8401dbf3ffb4f35bcc8e16f4a04cd7c.json"}}, {"family": "Rehm", "given": "Heidi L", "initials": "HL"}, {"family": "MacArthur", "given": "Daniel G", "initials": "DG"}, {"family": "O'Donnell-Luria", "given": "Anne", "initials": "A", "orcid": "0000-0001-6418-9592", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/00a7a6beb0be4ccb8b296330fa13cb3e.json"}}], "type": "journal article", "published": "2025-10-31", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "16", "issue": "1", "pages": "9623", "issn-l": "2041-1723"}, "abstract": "Incomplete penetrance, or absence of disease phenotype in an individual with a disease-associated variant, is a major challenge in variant interpretation. Studying individuals with apparent incomplete penetrance can shed light on underlying drivers of altered phenotype penetrance. Here, we investigate clinically relevant variants from ClinVar in 807,162 individuals from the Genome Aggregation Database (gnomAD), demonstrating improved representation in gnomAD version 4. We then conduct a comprehensive case-by-case assessment of 734 predicted loss of function variants in 77 genes associated with severe, early-onset, highly penetrant haploinsufficient disease. Here, we identify explanations for the presumed lack of disease manifestation in 701 of 734 variants (95%). Individuals with unexplained lack of disease manifestation in this set of disorders are rare, underscoring the need and power of deep case-by-case assessment presented here to minimize false assignments of disease risk, particularly in unaffected individuals with higher rates of secondary properties that result in rescue.", "doi": "10.1038/s41467-025-61698-x", "pmid": "41173899", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12579199"}, {"db": "pii", "key": "10.1038/s41467-025-61698-x"}], "notes": [], "created": "2026-08-20T08:53:57.705Z", "modified": "2026-08-20T08:53:57.915Z"}, {"entity": "publication", "iuid": "6745f8d56abc4c399713c87412f7757d", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/6745f8d56abc4c399713c87412f7757d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/6745f8d56abc4c399713c87412f7757d"}}, "title": "Exploring penetrance of clinically relevant variants in over 800,000 humans from the Genome Aggregation Database.", "authors": [{"family": "Gudmundsson", "given": "Sanna", "initials": "S", "orcid": "0000-0002-2332-074X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/167f305a31a3449c82851b262d13ee87.json"}}, {"family": "Singer-Berk", "given": "Moriel", "initials": "M"}, {"family": "Stenton", "given": "Sarah L", "initials": "SL"}, {"family": "Goodrich", "given": "Julia K", "initials": "JK"}, {"family": "Wilson", "given": "Michael W", "initials": "MW"}, {"family": "Einson", "given": "Jonah", "initials": "J"}, {"family": "Watts", "given": "Nicholas A", "initials": "NA"}, {"family": "Genome Aggregation Database Consortium", "given": "", "initials": ""}, {"family": "Lappalainen", "given": "Tuuli", "initials": "T"}, {"family": "Rehm", "given": "Heidi L", "initials": "HL"}, {"family": "MacArthur", "given": "Daniel G", "initials": "DG"}, {"family": "O'Donnell-Luria", "given": "Anne", "initials": "A", "orcid": "0000-0001-6418-9592", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/00a7a6beb0be4ccb8b296330fa13cb3e.json"}}], "type": "journal article", "published": "2024-06-13", "journal": {"title": "bioRxiv", "issn": "2692-8205", "issn-l": null}, "abstract": "Incomplete penetrance, or absence of disease phenotype in an individual with a disease-associated variant, is a major challenge in variant interpretation. Studying individuals with apparent incomplete penetrance can shed light on underlying drivers of altered phenotype penetrance. Here, we investigate clinically relevant variants from ClinVar in 807,162 individuals from the Genome Aggregation Database (gnomAD), demonstrating improved representation in gnomAD version 4. We then conduct a comprehensive case-by-case assessment of 734 predicted loss of function variants (pLoF) in 77 genes associated with severe, early-onset, highly penetrant haploinsufficient disease. We identified explanations for the presumed lack of disease manifestation in 701 of the variants (95%). Individuals with unexplained lack of disease manifestation in this set of disorders rarely occur, underscoring the need and power of deep case-by-case assessment presented here to minimize false assignments of disease risk, particularly in unaffected individuals with higher rates of secondary properties that result in rescue.", "doi": "10.1101/2024.06.12.593113", "pmid": "38915639", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11195293"}, {"db": "pii", "key": "2024.06.12.593113"}], "notes": [], "created": "2026-08-20T10:55:18.465Z", "modified": "2026-08-20T10:55:18.531Z"}, {"entity": "publication", "iuid": "06fd244769ac40d4816149ceb8bc2c14", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/06fd244769ac40d4816149ceb8bc2c14.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/06fd244769ac40d4816149ceb8bc2c14"}}, "title": "Amplification-free long read sequencing reveals unforeseen CRISPR-Cas9 off-target activity", "authors": [{"family": "H\u00f6ijer", "given": "Ida", "initials": "I", "orcid": "0000-0002-3915-3384", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fa1a8d7500f147cb852a2e9c3e8617c5.json"}}, {"family": "Johansson", "given": "Josefin", "initials": "J", "orcid": "0000-0002-5152-4096", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/89be12a9d71848bb945916cd936700f4.json"}}, {"family": "Gudmundsson", "given": "Sanna", "initials": "S", "orcid": "0000-0002-2332-074X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/167f305a31a3449c82851b262d13ee87.json"}}, {"family": "Chin", "given": "Chen Shan", "initials": "CS"}, {"family": "Bunikis", "given": "Ignas", "initials": "I"}, {"family": "H\u00e4ggqvist", "given": "Susana", "initials": "S"}, {"family": "Emmanouilidou", "given": "Anastasia", "initials": "A"}, {"family": "Wilbe", "given": "Maria", "initials": "M"}, {"family": "Hoed", "given": "Marcel den", "initials": "Md"}, {"family": "Bondeson", "given": "Marie Louise", "initials": "ML"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fbdc6712238248f28392139dacb6df99.json"}}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a8b8ce05cf7f49aeb3199b5938b9f160.json"}}], "type": "posted-content", "published": "2020-02-09", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2020.02.09.940486", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T09:55:56.955Z", "modified": "2026-08-20T09:55:57.128Z"}]}