VCV000290284.35 - ClinVar

NM_001130987.2(DYSF):c.4462C>T (p.Gln1488Ter)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(5)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001130987.2(DYSF):c.4462C>T (p.Gln1488Ter)

Variation ID: 290284 Accession: VCV000290284.35

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2p13.2 2: 71613408 (GRCh38) [ NCBI UCSC ] 2: 71840538 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Dec 6, 2016	Oct 20, 2024	Jul 6, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001130987.2:c.4462C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001124459.1:p.Gln1488Ter	nonsense
NM_003494.4:c.4408C>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_003485.1:p.Gln1470Ter	nonsense
NM_001130455.2:c.4411C>T	NP_001123927.1:p.Gln1471Ter	nonsense
NM_001130976.2:c.4366C>T	NP_001124448.1:p.Gln1456Ter	nonsense
NM_001130977.2:c.4366C>T	NP_001124449.1:p.Gln1456Ter	nonsense
NM_001130978.2:c.4408C>T	NP_001124450.1:p.Gln1470Ter	nonsense
NM_001130979.2:c.4501C>T	NP_001124451.1:p.Gln1501Ter	nonsense
NM_001130980.2:c.4459C>T	NP_001124452.1:p.Gln1487Ter	nonsense
NM_001130981.2:c.4459C>T	NP_001124453.1:p.Gln1487Ter	nonsense
NM_001130982.2:c.4504C>T	NP_001124454.1:p.Gln1502Ter	nonsense
NM_001130983.2:c.4411C>T	NP_001124455.1:p.Gln1471Ter	nonsense
NM_001130984.2:c.4369C>T	NP_001124456.1:p.Gln1457Ter	nonsense
NM_001130985.2:c.4462C>T	NP_001124457.1:p.Gln1488Ter	nonsense
NM_001130986.2:c.4369C>T	NP_001124458.1:p.Gln1457Ter	nonsense
NC_000002.12:g.71613408C>T
NC_000002.11:g.71840538C>T
NG_008694.1:g.164786C>T
LRG_845:g.164786C>T
LRG_845t1:c.4408C>T	LRG_845p1:p.Gln1470Ter
LRG_845t2:c.4462C>T	LRG_845p2:p.Gln1488Ter

... more HGVS ... less HGVS

Protein change

Q1488*, Q1470*, Q1456*, Q1457*, Q1501*, Q1502*, Q1487*, Q1471*

Other names

Canonical SPDI

NC_000002.12:71613407:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00000

The Genome Aggregation Database (gnomAD) 0.00001

Links

ClinGen: CA10606721 dbSNP: rs886044411 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
DYSF		-	-	GRCh38 GRCh37	4065	4114

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Autosomal recessive limb-girdle muscular dystrophy type 2B	Likely pathogenic (1)	no assertion criteria provided	Jun 22, 2017	RCV000306643.3
not provided	Pathogenic/Likely pathogenic (2)	criteria provided, multiple submitters, no conflicts	Jan 12, 2018	RCV000726457.26
Qualitative or quantitative defects of dysferlin	Pathogenic (1)	criteria provided, single submitter	Jun 28, 2023	RCV003736690.2
Miyoshi muscular dystrophy 1	Pathogenic (1)	criteria provided, single submitter	Jul 6, 2023	RCV003463778.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Jan 12, 2018)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000344805.4 First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DYSF Number of individuals with the variant: 2 Sex: mixed
Pathogenic (Jul 06, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Miyoshi muscular dystrophy 1 Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV004196498.1 First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023
Pathogenic (Jun 28, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Qualitative or quantitative defects of dysferlin Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004517950.1 First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024	Publications: PubMed (3) PubMed: 33610434‚ 17698709‚ 20301480 Comment: For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 290284). This premature translational stop signal … (more) For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 290284). This premature translational stop signal has been observed in individual(s) with DYSF-related conditions (PMID: 33610434). This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Gln1470*) in the DYSF gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DYSF are known to be pathogenic (PMID: 17698709, 20301480). (less)
Likely pathogenic (May 01, 2016)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV001152339.27 First in ClinVar: Feb 03, 2020 Last updated: Oct 20, 2024	Number of individuals with the variant: 1
Likely pathogenic (Jun 22, 2017)	no assertion criteria provided Method: clinical testing	Autosomal recessive limb-girdle muscular dystrophy type 2B Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000792411.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018	Publications: PubMed (1) PubMed: 27602406

Comment:

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 290284). This premature translational stop signal has been observed in individual(s) with DYSF-related conditions (PMID: 33610434). This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Gln1470*) in the DYSF gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DYSF are known to be pathogenic (PMID: 17698709, 20301480).

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Miyoshi myopathy and limb girdle muscular dystrophy R2 are the same disease.	Moore U	Neuromuscular disorders : NMD	2021	PMID: 33610434
Dysferlinopathy.	Adam MP	-	2021	PMID: 20301480
The Clinical Outcome Study for dysferlinopathy: An international multicenter study.	Harris E	Neurology. Genetics	2016	PMID: 27602406
Phenotypic study in 40 patients with dysferlin gene mutations: high frequency of atypical phenotypes.	Nguyen K	Archives of neurology	2007	PMID: 17698709
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DYSF	-	-	-	-

Text-mined citations for rs886044411 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_001130987.2(DYSF):c.4462C>T (p.Gln1488Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs886044411 ...