NM_001371596.2(MFSD8):c.1102+2T>C AND Neuronal ceroid lipofuscinosis 7

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Apr 11, 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:: RCV002954176.3

Allele description [Variation Report for NM_001371596.2(MFSD8):c.1102+2T>C]

NM_001371596.2(MFSD8):c.1102+2T>C

Gene:

MFSD8:major facilitator superfamily domain containing 8 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q28.2

Genomic location:

Preferred name:

NM_001371596.2(MFSD8):c.1102+2T>C

HGVS:

NC_000004.12:g.127921858A>G
NG_008657.1:g.49127T>C
NM_001363520.3:c.901+2T>C
NM_001363521.3:c.787+2T>C
NM_001371590.2:c.967+2T>C
NM_001371591.2:c.1102+2T>C
NM_001371592.2:c.1108+2T>C
NM_001371593.2:c.988+2T>C
NM_001371594.2:c.955+2T>C
NM_001371595.1:c.820+2T>C
NM_001371596.2:c.1102+2T>CMANE SELECT
NM_001410765.1:c.652+2T>C
NM_001410766.1:c.885-87T>C
NM_152778.4:c.1102+2T>C
LRG_833t1:c.1102+2T>C
LRG_833t2:c.1102+2T>C
LRG_833:g.49127T>C
NC_000004.11:g.128843013A>G

Molecular consequence:

NM_001410766.1:c.885-87T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001363520.3:c.901+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001363521.3:c.787+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001371590.2:c.967+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001371591.2:c.1102+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001371592.2:c.1108+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001371593.2:c.988+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001371594.2:c.955+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001371595.1:c.820+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001371596.2:c.1102+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001410765.1:c.652+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_152778.4:c.1102+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003280175	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Apr 11, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 32005694, 16199547, 19177532, 25227500, 28586915, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003280175

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Apr 11, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical exome sequencing as the first-tier test for diagnosing developmental disorders covering both CNV and SNV: a Chinese cohort.

Dong X, Liu B, Yang L, Wang H, Wu B, Liu R, Chen H, Chen X, Yu S, Chen B, Wang S, Xu X, Zhou W, Lu Y.

J Med Genet. 2020 Aug;57(8):558-566. doi: 10.1136/jmedgenet-2019-106377. Epub 2020 Jan 31.

PubMed [citation]

PMID:: 32005694
PMCID:: PMC7418612

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003280175.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This variant is present in population databases (no rsID available, gnomAD 0.003%). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 2068020). Disruption of this splice site has been observed in individual(s) with clinical features of MFSD8-related conditions (PMID: 32005694). This sequence change affects a donor splice site in intron 11 of the MFSD8 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MFSD8 are known to be pathogenic (PMID: 19177532, 25227500, 28586915).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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