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GRCh37/hg19 12q14.3(chr12:65716808-66690108)x1 AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 24, 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:
RCV003483155.1

Allele description [Variation Report for GRCh37/hg19 12q14.3(chr12:65716808-66690108)x1]

GRCh37/hg19 12q14.3(chr12:65716808-66690108)x1

Genes:
LLPH:LLP homolog, long-term synaptic facilitation factor [Gene - OMIM - HGNC]
HMGA2:high mobility group AT-hook 2 [Gene - OMIM - HGNC]
IRAK3:interleukin 1 receptor associated kinase 3 [Gene - OMIM - HGNC]
MSRB3:methionine sulfoxide reductase B3 [Gene - OMIM - HGNC]
TMBIM4:transmembrane BAX inhibitor motif containing 4 [Gene - OMIM - HGNC]
Variant type:
copy number loss
Cytogenetic location:
12q14.3
Genomic location:
Chr12: 65716808 - 66690108 (on Assembly GRCh37)
Preferred name:
GRCh37/hg19 12q14.3(chr12:65716808-66690108)x1
HGVS:

    Condition(s)

    Synonyms:
    none provided
    Identifiers:
    MedGen: C3661900

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    Assertion and evidence details

    Help
    Submission AccessionSubmitterReview Status
    (Assertion method)    		Clinical Significance
    (Last evaluated)    		OriginMethodCitations
    SCV004231672Quest Diagnostics Nichols Institute San Juan Capistrano
    criteria provided, single submitter

    (ACMG/ClinGen CNV Guidelines, 2019)    		Pathogenic
    (Sep 24, 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, SCV004231672.1

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

    Description

    The copy number loss of 12q14.3 involves multiple protein-coding genes, including HMGA2 (OMIM 600698). Haploinsufficiency of HMGA2 is associated with autosomal dominant Silver-Russell syndrome-5 (OMIM 618908, Meyer 2021, Mercadante 2020, Heldt 2018, Abi Habib 2018, Leszinski 2018, Spengler 2010, De Crescenzo 2015, Costain 2018, Fischetto 2017). There are no similar copy number losses of this region in the general populations of the Database of Genomic Variants. Thus, based on current medical literature and gene content, this copy number variant (CNV) is classified as pathogenic. References: Abi Habib et al., Genet Med. 2018 Feb;20(2):250-258. PMID: 28796236 Buysse et al., Eur J Med Genet. 2009 Mar-Jun;52(2-3):101-7. PMID: 19298872 Costain et al., Eur J Hum Genet. 2018 May;26(5):740-744. PMID: 29453418 De Crescenzo et al., J Hum Genet. 2015 Jun;60(6):287-93. PMID: 25809938 Fischetto et al., Am J Med Genet A. 2017 Jul;173(7):1922-1930. PMID: 28407409 Heldt et al., Eur J Med Genet. 2018 Aug;61(8):421-427. PMID: 29501611 Hubner et al., J Clin Endocrinol Metab. 2020 Jul 1;105(7):dgaa273. PMID: 32421827 Leszinski et al., Gene. 2018 Jul 15;663:110-114. PMID: 29655892. Mercadante et al., Ital J Pediatr. 2020 Jul 28;46(1):108. doi: 10.1186/s13052-020-00866-9. PMID: 32723361 Meyer et al., Orphanet J Rare Dis. 2021 Jan 22;16(1):42. PMID: 33482836 Spengler et al., J Med Genet. 2010 May;47(5):356-60. PMID: 19762329

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

    Last Updated: Feb 4, 2024