NM_001130987.2(DYSF):c.3228+1G>A AND Qualitative or quantitative defects of dysferlin

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 13, 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:: RCV001201509.5

Allele description [Variation Report for NM_001130987.2(DYSF):c.3228+1G>A]

NM_001130987.2(DYSF):c.3228+1G>A

Gene:

DYSF:dysferlin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p13.2

Genomic location:

Preferred name:

NM_001130987.2(DYSF):c.3228+1G>A

HGVS:

NC_000002.12:g.71570742G>A
NG_008694.1:g.122120G>A
NM_001130455.2:c.3177+1G>A
NM_001130976.2:c.3132+1G>A
NM_001130977.2:c.3132+1G>A
NM_001130978.2:c.3174+1G>A
NM_001130979.2:c.3267+1G>A
NM_001130980.2:c.3225+1G>A
NM_001130981.2:c.3225+1G>A
NM_001130982.2:c.3270+1G>A
NM_001130983.2:c.3177+1G>A
NM_001130984.2:c.3135+1G>A
NM_001130985.2:c.3228+1G>A
NM_001130986.2:c.3135+1G>A
NM_001130987.2:c.3228+1G>AMANE SELECT
NM_003494.4:c.3174+1G>A
LRG_845t1:c.3174+1G>A
LRG_845t2:c.3228+1G>A
LRG_845:g.122120G>A
NC_000002.11:g.71797872G>A
NM_003494.3:c.3174+1G>A

Links:

dbSNP: rs2092371566

NCBI 1000 Genomes Browser:

rs2092371566

Molecular consequence:

NM_001130455.2:c.3177+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130976.2:c.3132+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130977.2:c.3132+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130978.2:c.3174+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130979.2:c.3267+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130980.2:c.3225+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130981.2:c.3225+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130982.2:c.3270+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130983.2:c.3177+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130984.2:c.3135+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130985.2:c.3228+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130986.2:c.3135+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130987.2:c.3228+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_003494.4:c.3174+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Qualitative or quantitative defects of dysferlin
Synonyms:: Dysferlinopathy
Identifiers:: MONDO: MONDO:0016145; MedGen: C2931687

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pituitary adenylate cyclase-activating polypeptide preproprotein [Homo sapiens]
pituitary adenylate cyclase-activating polypeptide preproprotein [Homo sapiens]
gi|153266795|ref|NP_001108.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001372583	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 13, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16199547, 17698709, 20301480, 33715265, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001372583

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 13, 2023)

germline

clinical testing

PubMed (5)
[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

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

Phenotypic study in 40 patients with dysferlin gene mutations: high frequency of atypical phenotypes.

Nguyen K, Bassez G, Krahn M, Bernard R, Laforêt P, Labelle V, Urtizberea JA, Figarella-Branger D, Romero N, Attarian S, Leturcq F, Pouget J, Lévy N, Eymard B.

Arch Neurol. 2007 Aug;64(8):1176-82.

PubMed [citation]

PMID:: 17698709

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001372583.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change affects a donor splice site in intron 29 of the DYSF 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 DYSF are known to be pathogenic (PMID: 17698709, 20301480). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with DYSF-related conditions (PMID: 33715265; Invitae). ClinVar contains an entry for this variant (Variation ID: 933322). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	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: Feb 20, 2024

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