NM_000143.4(FH):c.1237-11C>G AND Hereditary leiomyomatosis and renal cell cancer

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 15, 2022
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:: RCV002266555.2

Allele description [Variation Report for NM_000143.4(FH):c.1237-11C>G]

NM_000143.4(FH):c.1237-11C>G

Gene:

FH:fumarate hydratase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q43

Genomic location:

Preferred name:

NM_000143.4(FH):c.1237-11C>G

HGVS:

NC_000001.11:g.241500601G>C
NG_012338.1:g.24154C>G
NM_000143.4:c.1237-11C>GMANE SELECT
LRG_504t1:c.1237-11C>G
LRG_504:g.24154C>G
NC_000001.10:g.241663901G>C
NM_000143.3:c.1237-11C>G

Links:

dbSNP: rs2147913449

NCBI 1000 Genomes Browser:

rs2147913449

Molecular consequence:

NM_000143.4:c.1237-11C>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Hereditary leiomyomatosis and renal cell cancer
Synonyms:: Reed syndrome; Multiple cutaneous and uterine leiomyomatosis; Cutaneous leiomyomata with uterine leiomyomata; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007888; MedGen: C1708350; Orphanet: 523; OMIM: 150800; Human Phenotype Ontology: HP:0007437

Recent activity

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Sahlingia subintegra isolate JAW4658 photosystem II reaction center protein D1 (...
Sahlingia subintegra isolate JAW4658 photosystem II reaction center protein D1 (psbA) gene, partial cds; chloroplast
gi|294713853|gb|GQ280888.1|

Nucleotide
Sahlingia subintegra isolate JAW3442 photosystem II reaction center protein D1 (...
Sahlingia subintegra isolate JAW3442 photosystem II reaction center protein D1 (psbA) gene, partial cds; chloroplast
gi|157092057|gb|EF660256.1|

Nucleotide
eli17
eli17

biosample
Elizabethkingia miricola DSM 14571
Elizabethkingia miricola DSM 14571

biosample
PREDICTED: Homo sapiens tRNA splicing endonuclease subunit 2 (TSEN2), transcript...
PREDICTED: Homo sapiens tRNA splicing endonuclease subunit 2 (TSEN2), transcript variant X25, mRNA
gi|2462592973|ref|XM_054348041.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002548547	Department of Molecular Diagnostics, Institute of Oncology Ljubljana	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 15, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 35806449, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002548547

Department of Molecular Diagnostics, Institute of Oncology Ljubljana

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 15, 2022)

germline

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	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification of Spliceogenic Variants beyond Canonical GT-AG Splice Sites in Hereditary Cancer Genes.

Dragoš VŠ, Strojnik K, Klančar G, Škerl P, Stegel V, Blatnik A, Banjac M, Krajc M, Novaković S.

Int J Mol Sci. 2022 Jul 4;23(13). doi:pii: 7446. 10.3390/ijms23137446.

PubMed [citation]

PMID:: 35806449
PMCID:: PMC9267136

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 Department of Molecular Diagnostics, Institute of Oncology Ljubljana, SCV002548547.1

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

Description

FH:c.1237-11C>G variant is absent from the large population studies (GnomAd). The variant is predicted to create a de novo donor splice site in exon 3 by in silico splicing tools. Functional RNA study has shown that the variant FH:c.1237-11C>G created a novel acceptor splice site, causing intron retention predicted to create an out-of-frame transcript (PMID: 35806449). The variant is not present in population database GnomAD. Therefore the variant was classified as likely pathogenic (ACMG/AMP: PM2, PP3, PS3-m, PP4)

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

Last Updated: Sep 16, 2024

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