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GRCh38/hg38 4q28.2(chr4:127964562-127965767)x0 AND Neuronal ceroid lipofuscinosis 7

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 24, 2023
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:
RCV003327719.2

Allele description [Variation Report for GRCh38/hg38 4q28.2(chr4:127964562-127965767)x0]

GRCh38/hg38 4q28.2(chr4:127964562-127965767)x0

Genes:
LOC129993058:ATAC-STARR-seq lymphoblastoid silent region 15678 [Gene]
ABHD18:abhydrolase domain containing 18 [Gene - HGNC]
MFSD8:major facilitator superfamily domain containing 8 [Gene - OMIM - HGNC]
Variant type:
copy number loss
Cytogenetic location:
4q28.2
Genomic location:
Chr4: 127964562 - 127965767 (on Assembly GRCh38)
Preferred name:
GRCh38/hg38 4q28.2(chr4:127964562-127965767)x0
HGVS:

    Condition(s)

    Name:
    Neuronal ceroid lipofuscinosis 7 (CLN7)
    Synonyms:
    MFSD8-Related Neuronal Ceroid-Lipofuscinosis
    Identifiers:
    MONDO: MONDO:0012588; MedGen: C1838571; Orphanet: 168491; Orphanet: 228366; OMIM: 610951

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    Assertion and evidence details

    Submission AccessionSubmitterReview Status
    (Assertion method)
    Clinical Significance
    (Last evaluated)
    OriginMethodCitations
    SCV004034167Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
    criteria provided, single submitter

    (ACMG/ClinGen CNV Guidelines, 2019)
    Uncertain significance
    (Aug 24, 2023)
    unknownresearch

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

    Summary from all submissions

    EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
    not providedunknownyesnot providednot providednot providednot providednot providedresearch

    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 Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV004034167.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedresearch PubMed (1)

    Description

    A homozygous deletion of exon 1 in MFSD8 (NM_001371596.2) was identified by exome sequencing in one individual with neuronal ceroid lipofuscinosis ([GRCh 38] chr4:127964562_127965767x0). These breakpoints have been estimated by exome sequencing only and therefore may not reflect the true breakpoints. Inheritance information is unavailable. The patient phenotype is nonspecific, but is consistent with cases described in the literature and/or published databases with overlapping variants. This intragenic variant deletes the first coding exon and is predicted to cause loss of the methionine initiation codon. This alteration is then predicted to lead to a truncated or absent protein. There is potential for rescue from a downstream methionine initiation codon. Loss of function of MFSD8 is an established disease mechanism in autosomal recessive neuronal ceroid lipofuscinosis (https://search.clinicalgenome.org/kb/gene-dosage). In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. The ACMG/ClinGen evidence codes and points used in this curation are as follows: 1: 0 points, 2: 0.45 points, A: 0 points, 4-5: 0.15 points; Total: 0.6 points; Riggs 2020 (PMID: 31690835).

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

    Last Updated: Mar 30, 2024