NM_001130987.2(DYSF):c.3957+1G>A AND Qualitative or quantitative defects of dysferlin

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 5, 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:: RCV002866449.3

Allele description [Variation Report for NM_001130987.2(DYSF):c.3957+1G>A]

NM_001130987.2(DYSF):c.3957+1G>A

Genes:

LOC122787137:CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:71829831-71831030 [Gene]
DYSF:dysferlin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p13.2

Genomic location:

Preferred name:

NM_001130987.2(DYSF):c.3957+1G>A

HGVS:

NC_000002.12:g.71602806G>A
NG_008694.1:g.154184G>A
NG_076966.2:g.206G>A
NM_001130455.2:c.3906+1G>A
NM_001130976.2:c.3861+1G>A
NM_001130977.2:c.3861+1G>A
NM_001130978.2:c.3903+1G>A
NM_001130979.2:c.3996+1G>A
NM_001130980.2:c.3954+1G>A
NM_001130981.2:c.3954+1G>A
NM_001130982.2:c.3999+1G>A
NM_001130983.2:c.3906+1G>A
NM_001130984.2:c.3864+1G>A
NM_001130985.2:c.3957+1G>A
NM_001130986.2:c.3864+1G>A
NM_001130987.2:c.3957+1G>AMANE SELECT
NM_003494.4:c.3903+1G>A
LRG_845t1:c.3903+1G>A
LRG_845t2:c.3957+1G>A
LRG_845:g.154184G>A
NC_000002.11:g.71829936G>A

Molecular consequence:

NM_001130455.2:c.3906+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130976.2:c.3861+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130977.2:c.3861+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130978.2:c.3903+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130979.2:c.3996+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130980.2:c.3954+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130981.2:c.3954+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130982.2:c.3999+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130983.2:c.3906+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130984.2:c.3864+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130985.2:c.3957+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130986.2:c.3864+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130987.2:c.3957+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_003494.4:c.3903+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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003227385	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Aug 5, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 17698709, 20301480, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003227385

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Aug 5, 2022)

germline

clinical testing

PubMed (4)
[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 (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003227385.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

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. This variant has not been reported in the literature in individuals affected with DYSF-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 36 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).

#	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

ClinVar

Relating variation to medicine