VCV001802250.3 - ClinVar

NM_001130987.2(DYSF):c.5680_5681insC (p.Asp1894fs)

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.

(1)

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

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001130987.2(DYSF):c.5680_5681insC (p.Asp1894fs)

Variation ID: 1802250 Accession: VCV001802250.3

Type and length

Insertion, 1 bp

Location

Cytogenetic: 2p13.2 2: 71669642-71669643 (GRCh38) [ NCBI UCSC ] 2: 71896772-71896773 (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 11, 2022	Dec 11, 2022	Sep 21, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_001130987.2:c.5680_5681insC MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001124459.1:p.Asp1894fs	frameshift
NM_003494.4:c.5563_5564insC MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_003485.1:p.Asp1855fs	frameshift
NM_001130455.2:c.5566_5567insC	NP_001123927.1:p.Asp1856fs	frameshift
NM_001130976.2:c.5521_5522insC	NP_001124448.1:p.Asp1841fs	frameshift
NM_001130977.2:c.5584_5585insC	NP_001124449.1:p.Asp1862fs	frameshift
NM_001130978.2:c.5626_5627insC	NP_001124450.1:p.Asp1876fs	frameshift
NM_001130979.2:c.5656_5657insC	NP_001124451.1:p.Asp1886fs	frameshift
NM_001130980.2:c.5614_5615insC	NP_001124452.1:p.Asp1872fs	frameshift
NM_001130981.2:c.5677_5678insC	NP_001124453.1:p.Asp1893fs	frameshift
NM_001130982.2:c.5659_5660insC	NP_001124454.1:p.Asp1887fs	frameshift
NM_001130983.2:c.5629_5630insC	NP_001124455.1:p.Asp1877fs	frameshift
NM_001130984.2:c.5587_5588insC	NP_001124456.1:p.Asp1863fs	frameshift
NM_001130985.2:c.5617_5618insC	NP_001124457.1:p.Asp1873fs	frameshift
NM_001130986.2:c.5524_5525insC	NP_001124458.1:p.Asp1842fs	frameshift
NC_000002.12:g.71669642_71669643insC
NC_000002.11:g.71896772_71896773insC
NG_008694.1:g.221020_221021insC
LRG_845:g.221020_221021insC
LRG_845t1:c.5563_5564insC	LRG_845p1:p.Asp1855fs
LRG_845t2:c.5680_5681insC	LRG_845p2:p.Asp1894fs

... more HGVS ... less HGVS

Protein change

D1841fs, D1842fs, D1855fs, D1856fs, D1862fs, D1863fs, D1872fs, D1873fs, D1876fs, D1877fs, D1886fs, D1887fs, D1893fs, D1894fs

Other names

Canonical SPDI

NC_000002.12:71669642::C

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.

Links

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	4062	4111

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 Distal myopathy with anterior tibial onset Miyoshi muscular dystrophy 1	Pathogenic (1)	criteria provided, single submitter	Sep 21, 2022	RCV002465063.3

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 (Sep 21, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Miyoshi muscular dystrophy 1 Autosomal recessive limb-girdle muscular dystrophy type 2B Distal myopathy with anterior tibial onset Affected status: yes Allele origin: unknown	Diagnostics Services (NGS), CSIR - Centre For Cellular And Molecular Biology Accession: SCV002759458.1 First in ClinVar: Dec 11, 2022 Last updated: Dec 11, 2022	Comment: The c.5680_5681insC variant is not present in publicly available population databases like 1000 Genomes, EVS, ExAC, gnomAD, Indian Exome Database or in our in-house exome … (more) The c.5680_5681insC variant is not present in publicly available population databases like 1000 Genomes, EVS, ExAC, gnomAD, Indian Exome Database or in our in-house exome database. The variant has neither been published nor reported to ClinVar, HGMD or OMIM, in any affected individuals. Other alternative variants at this position have been observed in affected individuals and reported to HGMD (IDs: CD1212208, CM116695). In silico pathogenicity prediction programs like SIFT, PolyPhen 2, Mutation Taster, CADD, Varsome, Franklin etc. predicted this variant to be likely deleterious. The variant causes a frameshift at the 1894th amino acid of the wild-type transcript, creating a translational premature stop signal at the 1903rd amino acid position of the altered transcript, which may either result in translation of a truncated protein or cause nonsense mediated decay of the mRNA.This individual harbours another pathogenic variant c.3095A>G in the DYSF gene, in heterozygous state (ClinVar accession: VCV000196175.12). (less) Number of individuals with the variant: 1 Secondary finding: no Method: exome sequencing

Comment:

The c.5680_5681insC variant is not present in publicly available population databases like 1000 Genomes, EVS, ExAC, gnomAD, Indian Exome Database or in our in-house exome database. The variant has neither been published nor reported to ClinVar, HGMD or OMIM, in any affected individuals. Other alternative variants at this position have been observed in affected individuals and reported to HGMD (IDs: CD1212208, CM116695). In silico pathogenicity prediction programs like SIFT, PolyPhen 2, Mutation Taster, CADD, Varsome, Franklin etc. predicted this variant to be likely deleterious. The variant causes a frameshift at the 1894th amino acid of the wild-type transcript, creating a translational premature stop signal at the 1903rd amino acid position of the altered transcript, which may either result in translation of a truncated protein or cause nonsense mediated decay of the mRNA.This individual harbours another pathogenic variant c.3095A>G in the DYSF gene, in heterozygous state (ClinVar accession: VCV000196175.12).

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

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for this variant ...

Record last updated Aug 06, 2023

ClinVar Genomic variation as it relates to human health

NM_001130987.2(DYSF):c.5680_5681insC (p.Asp1894fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...