NM_000133.4(F9):c.88+2T>C AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 9, 2021
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:: RCV001925914.3

Allele description

NM_000133.4(F9):c.88+2T>C

Gene:

F9:coagulation factor IX [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq27.1

Genomic location:

Preferred name:

NM_000133.4(F9):c.88+2T>C

HGVS:

NC_000023.11:g.139530854T>C
NG_007994.1:g.5119T>C
NM_000133.4:c.88+2T>CMANE SELECT
NM_001313913.2:c.88+2T>C
LRG_556:g.5119T>C
NC_000023.10:g.138613013T>C

Links:

dbSNP: rs2148353009

NCBI 1000 Genomes Browser:

rs2148353009

Molecular consequence:

NM_000133.4:c.88+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001313913.2:c.88+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Hereditary factor IX deficiency disease (HEMB)
Synonyms:: F9 DEFICIENCY; PLASMA THROMBOPLASTIN COMPONENT DEFICIENCY; Hemophilia B; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010604; MeSH: D002836; MedGen: C0008533; Orphanet: 98879; OMIM: 306900

Name:: Thrombophilia, X-linked, due to factor 9 defect
Synonyms:: Thrombophilia, X-linked, due to factor IX defect
Identifiers:: MONDO: MONDO:0010432; MedGen: C2749016; OMIM: 300807

Recent activity

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Homo sapiens uncoupling protein 1 (mitochondrial, proton carrier), mRNA (cDNA cl...
Homo sapiens uncoupling protein 1 (mitochondrial, proton carrier), mRNA (cDNA clone MGC:119953 IMAGE:40016003), complete cds
gi|68532512|gb|BC096736.1|

Nucleotide
Preimplantation Diagnosis
Preimplantation Diagnosis
Determination of the nature of a pathological condition or disease in the OVUM; ZYGOTE; or BLASTOCYST prior to implantation. CYTOGENETIC ANALYSIS is performed to determine the...<br/>Year introduced: 1998

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002180068	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 9, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 10090477, 10094553, 16199547, 20301668, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002180068

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 9, 2021)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

Citations

PubMed

Reported in vivo splice-site mutations in the factor IX gene: severity of splicing defects and a hypothesis for predicting deleterious splice donor mutations.

Ketterling RP, Drost JB, Scaringe WA, Liao DZ, Liu JZ, Kasper CK, Sommer SS.

Hum Mutat. 1999;13(3):221-31.

PubMed [citation]

PMID:: 10090477

Identification of twenty-one new mutations in the factor IX gene by SSCP analysis.

Montejo JM, Magallón M, Tizzano E, Solera J.

Hum Mutat. 1999;13(2):160-5.

PubMed [citation]

PMID:: 10094553

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV002180068.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant is also known as donor splice 119T>C. Disruption of this splice site has been observed in individuals with hemophilia B (PMID: 10090477, 10094553). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 1 of the F9 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in F9 are known to be pathogenic (PMID: 20301668).

#	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: Feb 28, 2024

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