NM_024301.5(FKRP):c.1415del (p.Lys472fs) AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 2, 2023
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:: RCV003163067.2

Allele description [Variation Report for NM_024301.5(FKRP):c.1415del (p.Lys472fs)]

NM_024301.5(FKRP):c.1415del (p.Lys472fs)

Gene:

FKRP:fukutin related protein [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

19q13.32

Genomic location:

Preferred name:

NM_024301.5(FKRP):c.1415del (p.Lys472fs)

HGVS:

NC_000019.10:g.46756865del
NG_008898.2:g.15820del
NM_001039885.3:c.1415del
NM_024301.5:c.1415delMANE SELECT
NP_001034974.1:p.Lys472fs
NP_077277.1:p.Lys472fs
LRG_761t1:c.1415del
LRG_761:g.15820del
LRG_761p1:p.Lys472fs
NC_000019.9:g.47260122del
NM_024301.4:c.1415delA

Protein change:

K472fs

Links:

dbSNP: rs1555739280

NCBI 1000 Genomes Browser:

rs1555739280

Molecular consequence:

NM_001039885.3:c.1415del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_024301.5:c.1415del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003870499	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Mar 2, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003870499

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Mar 2, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Ambry Genetics, SCV003870499.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The c.1415delA variant, located in coding exon 1 of the FKRP gene, results from a deletion of one nucleotide at nucleotide position 1415, causing a translational frameshift with a predicted alternate stop codon (p.K472Sfs*18). This alteration occurs at the 3' terminus of theFKRP gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 24 amino acids (~5%) of the protein. However, premature stop codons are typically deleterious in nature, a significant portion of the protein is affected, and the impacted region is critical for protein function (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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