VCV002499487.1 - ClinVar

NM_004006.3(DMD):c.6291-13537A>G

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.

Likely pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_004006.3(DMD):c.6291-13537A>G

Variation ID: 2499487 Accession: VCV002499487.1

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: Xp21.1 X: 32230600 (GRCh38) [ NCBI UCSC ] X: 32248717 (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	Apr 23, 2023	Apr 23, 2023	Apr 21, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NM_004006.3:c.6291-13537A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_000109.4:c.6267-13537A>G		intron variant
NM_004009.3:c.6279-13537A>G		intron variant
NM_004010.3:c.5922-13537A>G		intron variant
NM_004011.4:c.2268-13537A>G		intron variant
NM_004012.4:c.2259-13537A>G		intron variant
NC_000023.11:g.32230600T>C
NC_000023.10:g.32248717T>C
NG_012232.1:g.1114010A>G
LRG_199:g.1114010A>G

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000023.11:32230599:T: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.
DMD		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	9338	9631

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.
Becker muscular dystrophy	Likely pathogenic (1)	criteria provided, single submitter	Apr 21, 2021	RCV003223365.1

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.
Likely pathogenic (Apr 21, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Becker muscular dystrophy (X-linked recessive inheritance) Affected status: yes Allele origin: germline	Matsson lab, Uppsala university Accession: SCV003918209.1 First in ClinVar: Apr 23, 2023 Last updated: Apr 23, 2023	Comment: The c.6291-13537A>G variant was absent in gnomAD v2.1.1 and in silico tools predicts the creation of a cryptic splice site. Sequencing of RNA from a … (more) The c.6291-13537A>G variant was absent in gnomAD v2.1.1 and in silico tools predicts the creation of a cryptic splice site. Sequencing of RNA from a muscle biopsy indicated abberant splicing of the DMD gene and the creation of of a premature stop codon. Western blot analyses support a splicing defect showing strongly reduced full lenght dystrophin protein expression. In summary, the c.6291-13537A>G variant meets our criteria to be classified as likely pathogenic. (less) Clinical Features: Muscle weakness (present) , Elevated circulating creatine kinase concentration (present) , Difficulty walking (present) Sex: male Ethnicity/Population group: Caucasian Testing laboratory: Leids Universitaire Medisch Centrum Date variant was reported to submitter: 2021-04-21 Testing laboratory interpretation: not provided

Comment:

The c.6291-13537A>G variant was absent in gnomAD v2.1.1 and in silico tools predicts the creation of a cryptic splice site. Sequencing of RNA from a muscle biopsy indicated abberant splicing of the DMD gene and the creation of of a premature stop codon. Western blot analyses support a splicing defect showing strongly reduced full lenght dystrophin protein expression. In summary, the c.6291-13537A>G variant meets our criteria to be classified as likely pathogenic.

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 Apr 30, 2023

ClinVar Genomic variation as it relates to human health

NM_004006.3(DMD):c.6291-13537A>G

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...