NM_000128.4(F11):c.218+4A>G AND Hereditary factor XI deficiency disease

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jun 23, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000668645.3

Allele description [Variation Report for NM_000128.4(F11):c.218+4A>G]

NM_000128.4(F11):c.218+4A>G

Gene:

F11:coagulation factor XI [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q35.2

Genomic location:

Preferred name:

NM_000128.4(F11):c.218+4A>G

HGVS:

NC_000004.12:g.186271775A>G
NG_008051.1:g.10812A>G
NM_000128.4:c.218+4A>GMANE SELECT
NM_001354804.2:c.218+4A>G
LRG_583t1:c.218+4A>G
LRG_583:g.10812A>G
NC_000004.11:g.187192929A>G
NM_000128.3:c.218+4A>G

Links:

dbSNP: rs767240420

NCBI 1000 Genomes Browser:

rs767240420

Molecular consequence:

NM_000128.4:c.218+4A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001354804.2:c.218+4A>G - intron variant - [Sequence Ontology: SO:0001627]

Observations:

Condition(s)

Name:: Hereditary factor XI deficiency disease
Synonyms:: Plasma thromboplastin antecedent deficiency; PTA deficiency; Rosenthal syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012897; MeSH: D005173; MedGen: C0015523; Orphanet: 329; OMIM: 612416

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Synechocystis sp. PCC 6803 plasmid pSYSG DNA, complete genome
Synechocystis sp. PCC 6803 plasmid pSYSG DNA, complete genome
gi|38423799|dbj|AP004312.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000793279	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Aug 8, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV003935002	Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 23, 2023)	inherited	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27710856, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000793279

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Uncertain significance
(Aug 8, 2017)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link,

SCV003935002

Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 23, 2023)

inherited

clinical testing

PubMed (2)
[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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
South East Asian	inherited	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical and molecular epidemiology of factor XI deficiency in India.

Kawankar N, Rathi J, Ghosh K, Shetty S.

Thromb Res. 2016 Nov;147:85-87. doi: 10.1016/j.thromres.2016.09.022. Epub 2016 Sep 21. No abstract available.

PubMed [citation]

PMID:: 27710856

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Counsyl, SCV000793279.1

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

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

From Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, SCV003935002.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	South East Asian	1	not provided	not provided	clinical testing	PubMed (2)

Description

The homozygous c.218+4A>G intronic variant has been identified in a proband with low factor XI levels and has shown prolonged activated partial thromboplastin time. This variant has been observed in 0.0004% gnomAD (aggregated) database (PM2_Moderate). Splice site predictors have predicted to cause deleterious effect (PP3_moderate). PMID: 27710856 has reported this variant previously in 2016.

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

Last Updated: Mar 30, 2024

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