NM_001130987.2(DYSF):c.3113del (p.Pro1038fs) AND Autosomal recessive limb-girdle muscular dystrophy type 2B

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 3, 2018
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:: RCV001004952.2

Allele description [Variation Report for NM_001130987.2(DYSF):c.3113del (p.Pro1038fs)]

NM_001130987.2(DYSF):c.3113del (p.Pro1038fs)

Gene:

DYSF:dysferlin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2p13.2

Genomic location:

Preferred name:

NM_001130987.2(DYSF):c.3113del (p.Pro1038fs)

HGVS:

NC_000002.12:g.71570626del
NG_008694.1:g.122004del
NM_001130455.2:c.3062del
NM_001130976.2:c.3017del
NM_001130977.2:c.3017del
NM_001130978.2:c.3059del
NM_001130979.2:c.3152del
NM_001130980.2:c.3110del
NM_001130981.2:c.3110del
NM_001130982.2:c.3155del
NM_001130983.2:c.3062del
NM_001130984.2:c.3020del
NM_001130985.2:c.3113del
NM_001130986.2:c.3020del
NM_001130987.2:c.3113delMANE SELECT
NM_003494.4:c.3059del
NP_001123927.1:p.Pro1021fs
NP_001124448.1:p.Pro1006fs
NP_001124449.1:p.Pro1006fs
NP_001124450.1:p.Pro1020fs
NP_001124451.1:p.Pro1051fs
NP_001124452.1:p.Pro1037fs
NP_001124453.1:p.Pro1037fs
NP_001124454.1:p.Pro1052fs
NP_001124455.1:p.Pro1021fs
NP_001124456.1:p.Pro1007fs
NP_001124457.1:p.Pro1038fs
NP_001124458.1:p.Pro1007fs
NP_001124459.1:p.Pro1038fs
NP_003485.1:p.Pro1020fs
LRG_845t1:c.3059del
LRG_845t2:c.3113del
LRG_845:g.122004del
LRG_845p1:p.Pro1020fs
LRG_845p2:p.Pro1038fs
NC_000002.11:g.71797756del
p.Pro1038ArgfsTer37

Protein change:

P1006fs

Links:

dbSNP: rs753711667

NCBI 1000 Genomes Browser:

rs753711667

Molecular consequence:

NM_001130455.2:c.3062del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130976.2:c.3017del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130977.2:c.3017del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130978.2:c.3059del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130979.2:c.3152del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130980.2:c.3110del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130981.2:c.3110del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130982.2:c.3155del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130983.2:c.3062del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130984.2:c.3020del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130985.2:c.3113del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130986.2:c.3020del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130987.2:c.3113del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003494.4:c.3059del - 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

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Mus musculus wingless-type MMTV integration site family, member 7B (Wnt7b), tran...
Mus musculus wingless-type MMTV integration site family, member 7B (Wnt7b), transcript variant 1, mRNA
gi|254692921|ref|NM_009528.3|

Nucleotide
RecName: Full=Serine palmitoyltransferase 3; AltName: Full=Long chain base biosy...
RecName: Full=Serine palmitoyltransferase 3; AltName: Full=Long chain base biosynthesis protein 2b; Short=LCB2b; AltName: Full=Long chain base biosynthesis protein 3; Short=LCB 3; AltName: Full=Serine-palmitoyl-CoA transferase 3; Short=SPT 3
gi|158931158|sp|Q9NUV7.3|SPTC3_HUMA

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001164479	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 3, 2018)	germline	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001164479

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Dec 3, 2018)

germline

research

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	research

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 Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV001164479.1

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

Description

The homozygous p.Pro1038ArgfsTer37 variant in DYSF was identified by our study in one individual with limb-girdle muscular dystrophy (LGMD). This variant was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at position 1038 and leads to a premature termination codon 37 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the DYSF gene is an established disease mechanism for autosomal recessive LGMD, and this is a loss of function variant. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PM2, PVS1 (Richards 2015).

#	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: Mar 30, 2024

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