NM_001130987.2(DYSF):c.6305T>G (p.Phe2102Cys) AND Qualitative or quantitative defects of dysferlin

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 4, 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:: RCV003735535.3

Allele description [Variation Report for NM_001130987.2(DYSF):c.6305T>G (p.Phe2102Cys)]

NM_001130987.2(DYSF):c.6305T>G (p.Phe2102Cys)

Gene:

DYSF:dysferlin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p13.2

Genomic location:

Preferred name:

NM_001130987.2(DYSF):c.6305T>G (p.Phe2102Cys)

HGVS:

NC_000002.12:g.71682661T>G
NG_008694.1:g.234039T>G
NM_001130455.2:c.6191T>G
NM_001130976.2:c.6146T>G
NM_001130977.2:c.6209T>G
NM_001130978.2:c.6251T>G
NM_001130979.2:c.6281T>G
NM_001130980.2:c.6239T>G
NM_001130981.2:c.6302T>G
NM_001130982.2:c.6284T>G
NM_001130983.2:c.6254T>G
NM_001130984.2:c.6212T>G
NM_001130985.2:c.6242T>G
NM_001130986.2:c.6149T>G
NM_001130987.2:c.6305T>GMANE SELECT
NM_003494.4:c.6188T>G
NP_001123927.1:p.Phe2064Cys
NP_001124448.1:p.Phe2049Cys
NP_001124449.1:p.Phe2070Cys
NP_001124450.1:p.Phe2084Cys
NP_001124451.1:p.Phe2094Cys
NP_001124452.1:p.Phe2080Cys
NP_001124453.1:p.Phe2101Cys
NP_001124454.1:p.Phe2095Cys
NP_001124455.1:p.Phe2085Cys
NP_001124456.1:p.Phe2071Cys
NP_001124457.1:p.Phe2081Cys
NP_001124458.1:p.Phe2050Cys
NP_001124459.1:p.Phe2102Cys
NP_003485.1:p.Phe2063Cys
LRG_845t1:c.6188T>G
LRG_845t2:c.6305T>G
LRG_845:g.234039T>G
LRG_845p1:p.Phe2063Cys
LRG_845p2:p.Phe2102Cys
NC_000002.11:g.71909791T>G

Protein change:

F2049C

Molecular consequence:

NM_001130455.2:c.6191T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001130976.2:c.6146T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001130977.2:c.6209T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001130978.2:c.6251T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001130979.2:c.6281T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001130980.2:c.6239T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001130981.2:c.6302T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001130982.2:c.6284T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001130983.2:c.6254T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001130984.2:c.6212T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001130985.2:c.6242T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001130986.2:c.6149T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001130987.2:c.6305T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_003494.4:c.6188T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004512827	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Dec 4, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004512827

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Dec 4, 2023)

germline

clinical testing

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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004512827.2

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

Description

This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 2063 of the DYSF protein (p.Phe2063Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of DYSF-associated conditions (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DYSF protein function with a positive predictive value of 95%. 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.

#	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: Mar 5, 2025

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