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GRCh37/hg19 11p15.5(chr11:461373-2157956)x4 AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 13, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002473945.1

Allele description [Variation Report for GRCh37/hg19 11p15.5(chr11:461373-2157956)x4]

GRCh37/hg19 11p15.5(chr11:461373-2157956)x4

Genes:
  • BRSK2:BR serine/threonine kinase 2 [Gene - OMIM - HGNC]
  • CD151:CD151 molecule (Raph blood group) [Gene - OMIM - HGNC]
  • DEAF1:DEAF1 transcription factor [Gene - OMIM - HGNC]
  • EPS8L2:EPS8 like 2 [Gene - OMIM - HGNC]
  • H19:H19 imprinted maternally expressed transcript [Gene - OMIM - HGNC]
  • HRAS:HRas proto-oncogene, GTPase [Gene - OMIM - HGNC]
  • INS-IGF2:INS-IGF2 readthrough [Gene - HGNC]
  • LMNTD2-AS1:LMNTD2 antisense RNA 1 [Gene - HGNC]
  • MIR210HG:MIR210 host gene [Gene - HGNC]
  • MOB2:MOB kinase activator 2 [Gene - OMIM - HGNC]
  • PHRF1:PHD and ring finger domains 1 [Gene - OMIM - HGNC]
  • POLR2L:RNA polymerase II, I and III subunit L [Gene - OMIM - HGNC]
  • RASSF7:Ras association domain family member 7 [Gene - OMIM - HGNC]
  • AP2A2:adaptor related protein complex 2 subunit alpha 2 [Gene - OMIM - HGNC]
  • CDHR5:cadherin related family member 5 [Gene - OMIM - HGNC]
  • CRACR2B:calcium release activated channel regulator 2B [Gene - OMIM - HGNC]
  • CTSD:cathepsin D [Gene - OMIM - HGNC]
  • CEND1:cell cycle exit and neuronal differentiation 1 [Gene - OMIM - HGNC]
  • CHID1:chitinase domain containing 1 [Gene - OMIM - HGNC]
  • DRD4:dopamine receptor D4 [Gene - OMIM - HGNC]
  • DUSP8:dual specificity phosphatase 8 [Gene - OMIM - HGNC]
  • GATD1:glutamine amidotransferase class 1 domain containing 1 [Gene - HGNC]
  • IGF2:insulin like growth factor 2 [Gene - OMIM - HGNC]
  • IFITM10:interferon induced transmembrane protein 10 [Gene - OMIM - HGNC]
  • IRF7:interferon regulatory factor 7 [Gene - OMIM - HGNC]
  • KRTAP5-1:keratin associated protein 5-1 [Gene - OMIM - HGNC]
  • KRTAP5-2:keratin associated protein 5-2 [Gene - HGNC]
  • KRTAP5-3:keratin associated protein 5-3 [Gene - HGNC]
  • KRTAP5-4:keratin associated protein 5-4 [Gene - HGNC]
  • KRTAP5-5:keratin associated protein 5-5 [Gene - HGNC]
  • KRTAP5-6:keratin associated protein 5-6 [Gene - HGNC]
  • LMNTD2:lamin tail domain containing 2 [Gene - HGNC]
  • LRRC56:leucine rich repeat containing 56 [Gene - OMIM - HGNC]
  • LSP1:lymphocyte specific protein 1 [Gene - OMIM - HGNC]
  • MIR210:microRNA 210 [Gene - OMIM - HGNC]
  • MRPL23:mitochondrial ribosomal protein L23 [Gene - OMIM - HGNC]
  • MUC2:mucin 2, oligomeric mucus/gel-forming [Gene - OMIM - HGNC]
  • MUC5AC:mucin 5AC, oligomeric mucus/gel-forming [Gene - OMIM - HGNC]
  • MUC5B:mucin 5B, oligomeric mucus/gel-forming [Gene - OMIM - HGNC]
  • MUC6:mucin 6, oligomeric mucus/gel-forming [Gene - OMIM - HGNC]
  • PIDD1:p53-induced death domain protein 1 [Gene - OMIM - HGNC]
  • PNPLA2:patatin like phospholipase domain containing 2 [Gene - OMIM - HGNC]
  • PTDSS2:phosphatidylserine synthase 2 [Gene - OMIM - HGNC]
  • RNH1:ribonuclease/angiogenin inhibitor 1 [Gene - OMIM - HGNC]
  • RPLP2:ribosomal protein lateral stalk subunit P2 [Gene - OMIM - HGNC]
  • SCT:secretin [Gene - OMIM - HGNC]
  • SLC25A22:solute carrier family 25 member 22 [Gene - OMIM - HGNC]
  • SYT8:synaptotagmin 8 [Gene - OMIM - HGNC]
  • TSPAN4:tetraspanin 4 [Gene - OMIM - HGNC]
  • TOLLIP:toll interacting protein [Gene - OMIM - HGNC]
  • TALDO1:transaldolase 1 [Gene - OMIM - HGNC]
  • TMEM80:transmembrane protein 80 [Gene - OMIM - HGNC]
  • TNNI2:troponin I2, fast skeletal type [Gene - OMIM - HGNC]
  • TNNT3:troponin T3, fast skeletal type [Gene - OMIM - HGNC]
Variant type:
copy number gain
Cytogenetic location:
11p15.5
Genomic location:
Chr11: 461373 - 2157956 (on Assembly GRCh37)
Preferred name:
GRCh37/hg19 11p15.5(chr11:461373-2157956)x4
HGVS:

    Condition(s)

    Synonyms:
    none provided
    Identifiers:
    MedGen: CN517202

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    Assertion and evidence details

    Help
    Submission AccessionSubmitterReview Status
    (Assertion method)    		Clinical Significance
    (Last evaluated)    		OriginMethodCitations
    SCV002773811Quest Diagnostics Nichols Institute San Juan Capistrano
    criteria provided, single submitter

    (ACMG/ClinGen CNV Guidelines, 2019)    		Pathogenic
    (Apr 13, 2022)     		unknownclinical testing

    PubMed (1)
    [See all records that cite this PMID]

    Help

    Summary from all submissions

    EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
    not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

    Citations

    PubMed

    Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen).

    Riggs ER, Andersen EF, Cherry AM, Kantarci S, Kearney H, Patel A, Raca G, Ritter DI, South ST, Thorland EC, Pineda-Alvarez D, Aradhya S, Martin CL.

    Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6. Erratum in: Genet Med. 2021 Nov;23(11):2230. doi: 10.1038/s41436-021-01150-9.

    PubMed [citation]
    PMID:
    31690835
    PMCID:
    PMC7313390

    Details of each submission

    From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV002773811.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedclinical testing PubMed (1)

    Description

    The copy number gain at 11p15.5 involves numerous protein-coding genes and overlaps the imprinting control region 1 (ICR1), which regulates the expression of IGF2 (expressed on the paternal allele) and H19 (expressed on the maternal allele). Please note that, the imprinting control region 2 (ICR2), which regulates the expression of CDKN1C, KCNQ10T1, and KCNQ1, is NOT involved in this copy number gain. Duplications of 11p15.5 can cause either Beckwith-Wiedemann syndrome (OMIM 130650) or Silver-Russell syndrome (SRS, OMIM 180860), depending on the parent of origin for the duplicated chromosome 11 segment. Russell-Silver syndrome (RSS) is characterized by intrauterine growth etardation accompanied by postnatal growth deficiency. Maternally derived duplications of 11p15.5 are associated with SRS (GeneReviews [Internet]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1324/). Beckwith-Wiedemann syndrome (BWS), is a growth disorder variably characterized by neonatal hypoglycemia, macrosomia, macroglossia, hemihyperplasia, omphalocele, embryonal tumors (e.g., Wilms tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma), visceromegaly, adrenocortical cytomegaly, renal abnormalities, and ear creases/pits. Paternally derived duplications of 11p15.5 are associated with BWS (GeneReviews [Internet]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1394/). In the literature there are several reports of individuals with Beckwith-Wiedemann syndrome and duplications that overlap only IC1, not IC2. These duplications have arisen on the paternal allele, and typically methylation of IC1 was increased, while methylation of IC2 was normal (Wang 29270226; Baskin 24154661; Heide 29223973). Additionally, one patient was reported to have a triplication of the IC1 interval that falls almost entirely within the current interval, and the proband expressed the expected Beckwith-Wiedemann syndrome phenotype. Consistent with imprinting patterns, her father who had transmitted the triplication, and had inherited it maternally, displayed characteristics of Silver-Russell syndrome (Jurkiewicz 2017). There are no similar copy number gains of this region in the general populations of the Database of Genomic Variants. Thus, the clinical significance of this copy number variant (CNV) is pathogenic. References: Baskin et al., Hum Genet. 2014 Mar;133(3):321-30. PMID: 24154661. Heide et al., J Med Genet. 2018 Mar;55(3):205-213. PMID: 29223973. Jurkiewicz et al., Am J Med Genet A. 2017 Jan;173(1):72-78. PMID: 27612309. Wang et al., Mol Cytogenet. 2017 Dec 19;10:46. PMID: 29270226.

    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

    Last Updated: Mar 26, 2023