ClinVar Miner

Submissions for variant NM_013275.6(ANKRD11):c.1903_1907del (p.Lys635fs)

dbSNP: rs886041125
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Total submissions: 33
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000406838 SCV000329064 pathogenic not provided 2022-02-24 criteria provided, single submitter clinical testing Frameshift 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: 27605097, 25833229, 28191890, 29158550, 32581362, 25413698, 25424714, 27667800, 25533962, 25363768, 28250421, 28449295, 28135719, 29530238, 31332282, 33048330, 32124548, 32371413, 31981491, 33955014, 33767182)
Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg RCV000496332 SCV000586701 pathogenic KBG syndrome 2017-08-01 criteria provided, single submitter clinical testing De novo LOF variant in a patient with feeding difficulties, short stature, microcephaly, moderate to severe ID, facial freckling.
Center of Genomic medicine, Geneva, University Hospital of Geneva RCV000496332 SCV000598143 pathogenic KBG syndrome 2016-10-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV000624014 SCV000741382 pathogenic Inborn genetic diseases 2016-03-30 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000626912 SCV000747615 likely pathogenic Global developmental delay; Ptosis; Clinodactyly of the 5th finger; Conductive hearing impairment; Intellectual disability; Short foot; Short palm; Unilateral cryptorchidism 2017-01-01 criteria provided, single submitter clinical testing
Baylor Genetics RCV000496332 SCV000807329 pathogenic KBG syndrome 2021-09-20 criteria provided, single submitter clinical testing
Genomic Medicine Lab, University of California San Francisco RCV000496332 SCV001167576 pathogenic KBG syndrome 2018-03-08 criteria provided, single submitter clinical testing
Invitae RCV000496332 SCV001222998 pathogenic KBG syndrome 2023-11-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys635Glnfs*26) in the ANKRD11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ANKRD11 are known to be pathogenic (PMID: 21782149, 25125236, 25413698, 25652421). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with KBG syndrome (PMID: 25533962, 25833229, 27605097, 27667800, 28250421, 28449295; Invitae). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 279678). For these reasons, this variant has been classified as Pathogenic.
Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital RCV000496332 SCV001423630 pathogenic KBG syndrome 2019-03-11 criteria provided, single submitter clinical testing [ACMG/AMP: PVS1, PS2, PM2, PS4_Moderate, PP1, PP5] This alteration is a null variant in a gene where LOF is a known mechanism of disease [PVS1], is de novo in origin as it was not detected in the submitted parental specimens (identity confirmed) [PS2], is absent from or rarely observed in large-scale population databases [PM2], has previously been observed in multiple unrelated patients with the same phenotype [PS4_Moderate], has been shown to cosegregate with disease in multiple affected family members [PP1], was reported as a pathogenic/likely pathogenic alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory) [PP5].
Institute of Human Genetics, University of Leipzig Medical Center RCV000496332 SCV001429285 pathogenic KBG syndrome 2019-06-05 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000406838 SCV001446926 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Knight Diagnostic Laboratories, Oregon Health and Sciences University RCV000496332 SCV001449014 pathogenic KBG syndrome 2019-07-08 criteria provided, single submitter clinical testing
Institute for Human Genetics, University Hospital Essen RCV001376679 SCV001478038 pathogenic Global developmental delay 2021-01-22 criteria provided, single submitter research
Génétique des Maladies du Développement, Hospices Civils de Lyon RCV001249513 SCV001593256 pathogenic Intellectual disability 2021-05-12 criteria provided, single submitter clinical testing de novo truncating variant absent from gnomAD. ALready pathogenic in ClinVar
CeGaT Center for Human Genetics Tuebingen RCV000406838 SCV001747176 pathogenic not provided 2023-12-01 criteria provided, single submitter clinical testing ANKRD11: PS2:Very Strong, PVS1, PM2, PS4:Moderate
Genomics England Pilot Project, Genomics England RCV000496332 SCV001760384 pathogenic KBG syndrome criteria provided, single submitter clinical testing
Blueprint Genetics RCV000406838 SCV001832255 pathogenic not provided 2019-09-23 criteria provided, single submitter clinical testing
Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano RCV000496332 SCV002097368 pathogenic KBG syndrome 2021-11-01 criteria provided, single submitter research
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV002274005 SCV002558912 pathogenic Neurodevelopmental delay criteria provided, single submitter clinical testing
3billion RCV000496332 SCV002573020 pathogenic KBG syndrome 2022-09-01 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Frameshift variant is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000279678 / PMID: 25413698). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
MGZ Medical Genetics Center RCV000496332 SCV002580668 pathogenic KBG syndrome 2022-02-01 criteria provided, single submitter clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV000496332 SCV003807633 pathogenic KBG syndrome 2022-10-21 criteria provided, single submitter clinical testing ACMG classification criteria: PVS1 very strong, PS4 strong, PM2 supporting, PM6 moderated
Revvity Omics, Revvity RCV000496332 SCV003817385 pathogenic KBG syndrome 2021-12-27 criteria provided, single submitter clinical testing
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV000496332 SCV004046188 pathogenic KBG syndrome criteria provided, single submitter clinical testing This frameshifting variant in exon 9 of 13 is predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been previously reported as a heterozygous familial and de novo change in patients with KBG syndrome (PMID: 27667800, 28449295, 27605097, 25533962, 28250421). The c.1903_1907del (p.Lys635GlnfsTer26) variant is absent from the gnomAD population database and thus is presumed to be rare. This result was confirmed by orthogonal testing. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.1903_1907del (p.Lys635GlnfsTer26) variant is classified as Pathogenic.
Laboratory of Medical Genetics, University of Torino RCV000496332 SCV004171097 pathogenic KBG syndrome criteria provided, single submitter clinical testing
Molecular Genetics Lab, CHRU Brest RCV000496332 SCV004697661 pathogenic KBG syndrome criteria provided, single submitter clinical testing
GeneReviews RCV000496332 SCV000778368 not provided KBG syndrome no assertion provided literature only
NIHR Bioresource Rare Diseases, University of Cambridge RCV001003618 SCV001162029 pathogenic Global developmental delay; Seizure; Abnormal facial shape; Conductive hearing impairment; Delayed speech and language development no assertion criteria provided research
Diagnostic Laboratory, Strasbourg University Hospital RCV001249513 SCV001423503 pathogenic Intellectual disability 2016-12-01 no assertion criteria provided clinical testing
Service de Génétique Moléculaire, Hôpital Robert Debré RCV001256985 SCV001433531 pathogenic Rare genetic intellectual disability no assertion criteria provided clinical testing
Autoinflammatory diseases unit, CHU de Montpellier RCV000496332 SCV001438084 pathogenic KBG syndrome 2014-12-15 no assertion criteria provided clinical testing
Service de Génétique Moléculaire, Hôpital Robert Debré RCV000496332 SCV001450672 pathogenic KBG syndrome 2020-08-31 no assertion criteria provided clinical testing
Clinical Genetics Laboratory, University Hospital Schleswig-Holstein RCV000496332 SCV002583321 pathogenic KBG syndrome 2021-11-02 no assertion criteria provided clinical testing

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