NM_001130987.2(DYSF):c.1258del (p.Ala420fs) AND Autosomal recessive limb-girdle muscular dystrophy type 2B

Germline classification:: Likely pathogenic (1 submission)
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:: RCV004555622.2

Allele description [Variation Report for NM_001130987.2(DYSF):c.1258del (p.Ala420fs)]

NM_001130987.2(DYSF):c.1258del (p.Ala420fs)

Gene:

DYSF:dysferlin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2p13.2

Genomic location:

Preferred name:

NM_001130987.2(DYSF):c.1258del (p.Ala420fs)

Other names:

NM_001130987.2(DYSF):c.1258del; p.Ala420fs

HGVS:

NC_000002.12:g.71526328del
NG_008694.1:g.77706del
NM_001130455.2:c.1165del
NM_001130976.2:c.1162del
NM_001130977.2:c.1162del
NM_001130978.2:c.1162del
NM_001130979.2:c.1255del
NM_001130980.2:c.1255del
NM_001130981.2:c.1255del
NM_001130982.2:c.1258del
NM_001130983.2:c.1165del
NM_001130984.2:c.1165del
NM_001130985.2:c.1258del
NM_001130986.2:c.1165del
NM_001130987.2:c.1258delMANE SELECT
NM_003494.4:c.1162del
NP_001123927.1:p.Ala389fs
NP_001124448.1:p.Ala388fs
NP_001124449.1:p.Ala388fs
NP_001124450.1:p.Ala388fs
NP_001124451.1:p.Ala419fs
NP_001124452.1:p.Ala419fs
NP_001124453.1:p.Ala419fs
NP_001124454.1:p.Ala420fs
NP_001124455.1:p.Ala389fs
NP_001124456.1:p.Ala389fs
NP_001124457.1:p.Ala420fs
NP_001124458.1:p.Ala389fs
NP_001124459.1:p.Ala420fs
NP_003485.1:p.Ala388fs
LRG_845t1:c.1162del
LRG_845t2:c.1258del
LRG_845:g.77706del
LRG_845p1:p.Ala388fs
LRG_845p2:p.Ala420fs
NC_000002.11:g.71753456del
NC_000002.11:g.71753458del
NM_001130987.2:c.1258del

Protein change:

A388fs

Links:

dbSNP: rs779969348

NCBI 1000 Genomes Browser:

rs779969348

Molecular consequence:

NM_001130455.2:c.1165del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130976.2:c.1162del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130977.2:c.1162del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130978.2:c.1162del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130979.2:c.1255del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130980.2:c.1255del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130981.2:c.1255del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130982.2:c.1258del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130983.2:c.1165del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130984.2:c.1165del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130985.2:c.1258del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130986.2:c.1165del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130987.2:c.1258del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003494.4:c.1162del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Autosomal recessive limb-girdle muscular dystrophy type 2B (LGMDR2)
Synonyms:: Limb-girdle muscular dystrophy, type 2B; Muscular dystrophy, limb-girdle, type 3; MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 2
Identifiers:: MONDO: MONDO:0009676; MedGen: C1850889; Orphanet: 268; OMIM: 253601

Recent activity

Clear Turn Off Turn On

wdr74 WD repeat domain 74 [Danio rerio]
wdr74 WD repeat domain 74 [Danio rerio]
Gene ID:558996

Gene

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
SCV005044806	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	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

SCV005044806

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Neuberg Centre For Genomic Medicine, NCGM, SCV005044806.2

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

Description

The frameshift c.1258del p.Ala420ProfsTer11 variant in DYSF gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Ala420ProfsTer11 variant is reported with allele frequency of 0.002% in gnomAD Exomes and is novel not in any individuals in 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic. This variant causes a frameshift starting with codon Alanine 420, changes this amino acid to Proline residue, and creates a premature Stop codon at position 11 of the new reading frame, denoted p.Ala420ProfsTer11. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. However, additional functional studies will be required to prove the pathogenicity of this variant. For these reasons, 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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 20, 2024

ClinVar

Relating variation to medicine