NM_000132.4(F8):c.5914_5915del (p.Ile1972fs) AND Hereditary factor VIII deficiency disease

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 1, 2019
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:: RCV001001337.8

Allele description [Variation Report for NM_000132.4(F8):c.5914_5915del (p.Ile1972fs)]

NM_000132.4(F8):c.5914_5915del (p.Ile1972fs)

Gene:

F8:coagulation factor VIII [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_000132.4(F8):c.5914_5915del (p.Ile1972fs)

HGVS:

NC_000023.11:g.154903989_154903990del
NG_011403.2:g.123734_123735del
NM_000132.4:c.5914_5915delMANE SELECT
NP_000123.1:p.Ile1972fs
LRG_555t1:c.5914_5915del
LRG_555:g.123734_123735del
LRG_555p1:p.Ile1972fs
NC_000023.10:g.154132264_154132265del
NC_000023.10:g.154132264_154132265delAT
NG_011403.1:g.123734_123735del

Protein change:

I1972fs

Links:

dbSNP: rs1216878586

NCBI 1000 Genomes Browser:

rs1216878586

Molecular consequence:

NM_000132.4:c.5914_5915del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary factor VIII deficiency disease (HEMA)
Synonyms:: AUTOSOMAL HEMOPHILIA A; Hemophilia A; Hemophilia A, congenital; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010602; MedGen: C0019069; Orphanet: 98878; OMIM: 306700

Recent activity

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BioProject
nsv600289 AND (alive[prop]) (0)
Gene
Spirosoma arboris strain HMF4905, whole genome shotgun sequencing project
Spirosoma arboris strain HMF4905, whole genome shotgun sequencing project
gi|1784013339|gb|WPIN00000000.1|WPI 0000

Nucleotide
Mucilaginibacter arboris strain HMF7410, whole genome shotgun sequencing project
Mucilaginibacter arboris strain HMF7410, whole genome shotgun sequencing project
gi|1784014161|gb|WPIK00000000.1|WPI 0000

Nucleotide
Paramyxovirus PREDICT_PMV-171 clone 10185 RNA-dependent RNA polymerase gene, par...
Paramyxovirus PREDICT_PMV-171 clone 10185 RNA-dependent RNA polymerase gene, partial cds
gi|2243706025|gb|MT125231.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001158527	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Pathogenic (Jun 1, 2019)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001158527

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Pathogenic
(Jun 1, 2019)

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 ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001158527.1

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

Description

The F8 c.5914_5915delAT; p.Ile1972fs variant, also known as del2 in Ile1953, is reported in the literature in individuals affected with severe hemophilia A (Johnsen 2017, Liu 2002). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by deleting two nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Johnsen JM et al. Novel approach to genetic analysis and results in 3000 hemophilia patients enrolled in the My Life, Our Future initiative. Blood Adv. 2017 May 18;1(13):824-834. Liu ML et al. Non-inversion factor VIII mutations in 80 hemophilia A families including 24 with alloimmune responses. Thromb Haemost. 2002 Feb;87(2):273-6.

#	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 26, 2024

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