VCV001700573.3 - ClinVar

NM_024301.5(FKRP):c.1327G>A (p.Glu443Lys)

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.

(2)

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_024301.5(FKRP):c.1327G>A (p.Glu443Lys)

Variation ID: 1700573 Accession: VCV001700573.3

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 19q13.32 19: 46756777 (GRCh38) [ NCBI UCSC ] 19: 47260034 (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	Feb 13, 2023	Dec 30, 2023	Jun 11, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_024301.5:c.1327G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_077277.1:p.Glu443Lys	missense
NM_001039885.3:c.1327G>A	NP_001034974.1:p.Glu443Lys	missense
NC_000019.10:g.46756777G>A
NC_000019.9:g.47260034G>A
NG_008898.2:g.15732G>A
LRG_761:g.15732G>A
LRG_761t1:c.1327G>A	LRG_761p1:p.Glu443Lys

... more HGVS ... less HGVS

Protein change

E443K

Other names

Canonical SPDI

NC_000019.10:46756776:G:A

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.
FKRP		-	-	GRCh38 GRCh37	1056	1100

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.
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5	Likely pathogenic (1)	criteria provided, single submitter	Jun 11, 2023	RCV003471303.1
Autosomal recessive limb-girdle muscular dystrophy type 2I	Likely pathogenic (1)	no assertion criteria provided	Aug 8, 2022	RCV003107986.3

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.
Likely pathogenic (Jun 11, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5 Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV004197420.1 First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023
Likely pathogenic (Aug 08, 2022)	no assertion criteria provided Method: clinical testing	Autosomal recessive limb-girdle muscular dystrophy type 2I (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Department of Medical Genetics, National Institute of Health Accession: SCV002558808.1 First in ClinVar: Feb 13, 2023 Last updated: Feb 13, 2023	Comment: We investigated an eleven-year-old Moroccan consanguineous female, with no particular familial history. The first clinical signs started with a frequent fall and calf hypertrophy at … (more) We investigated an eleven-year-old Moroccan consanguineous female, with no particular familial history. The first clinical signs started with a frequent fall and calf hypertrophy at 4 of age. The patient still walks on tiptoes and is not mentally retarded. Her serum creatine kinase (CK) level was 20 times increased from normal range. Electromyography (EMG) showed a myogenic pattern in muscles of upper and lower limbs. A Next-Generation Sequencing analysis (NGS) was performed for our patient. Two variants were detected in exon 4 of the FKRP gene including a new variant never reported in databases: NM_024301.5(FKRP):c.1364C>A; p.Ala455Asp known as pathogenic and NM_024301.5(FKRP):c.1327G>A. Direct Sanger sequencing showed that each one of the patient’s parents harbors one of the two mutations at heterozygous state. (less) Age: 10-19 years Sex: female Ethnicity/Population group: Moroccan

Comment:

We investigated an eleven-year-old Moroccan consanguineous female, with no particular familial history. The first clinical signs started with a frequent fall and calf hypertrophy at 4 of age. The patient still walks on tiptoes and is not mentally retarded. Her serum creatine kinase (CK) level was 20 times increased from normal range. Electromyography (EMG) showed a myogenic pattern in muscles of upper and lower limbs. A Next-Generation Sequencing analysis (NGS) was performed for our patient. Two variants were detected in exon 4 of the FKRP gene including a new variant never reported in databases: NM_024301.5(FKRP):c.1364C>A; p.Ala455Asp known as pathogenic and NM_024301.5(FKRP):c.1327G>A. Direct Sanger sequencing showed that each one of the patient’s parents harbors one of the two mutations at heterozygous state.

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 Jun 23, 2024

ClinVar Genomic variation as it relates to human health

NM_024301.5(FKRP):c.1327G>A (p.Glu443Lys)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...