NM_001174089.2(SLC4A11):c.425_433delinsC (p.Arg142fs) AND Congenital hereditary endothelial dystrophy of cornea

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 29, 2014
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:: RCV000190625.5

Allele description [Variation Report for NM_001174089.2(SLC4A11):c.425_433delinsC (p.Arg142fs)]

NM_001174089.2(SLC4A11):c.425_433delinsC (p.Arg142fs)

Gene:

SLC4A11:solute carrier family 4 member 11 [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

20p13

Genomic location:

Preferred name:

NM_001174089.2(SLC4A11):c.425_433delinsC (p.Arg142fs)

HGVS:

NC_000020.11:g.3234173_3234181delinsG
NG_017072.1:g.10061_10069delinsC
NM_001174089.2:c.425_433delinsCMANE SELECT
NM_001174090.2:c.554_562delinsC
NM_001363745.2:c.425_433delinsC
NM_032034.4:c.473_481delinsC
NP_001167560.1:p.Arg142fs
NP_001167561.1:p.Arg185fs
NP_001350674.1:p.Arg142fs
NP_114423.1:p.Arg158fs
NC_000020.10:g.3214819_3214827delinsG
NM_032034.3:c.473_481delinsC
NR_135000.1:n.593_601delinsC

Protein change:

R142fs

Links:

dbSNP: rs797045107

NCBI 1000 Genomes Browser:

rs797045107

Molecular consequence:

NM_001174089.2:c.425_433delinsC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001174090.2:c.554_562delinsC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001363745.2:c.425_433delinsC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_032034.4:c.473_481delinsC - frameshift variant - [Sequence Ontology: SO:0001589]
NR_135000.1:n.593_601delinsC - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Congenital hereditary endothelial dystrophy of cornea
Synonyms:: Corneal dystrophy, congenital hereditary endothelial; Congenital hereditary endothelial dystrophy of the cornea; Maumenee corneal dystrophy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009019; MedGen: C1857569; Orphanet: 293603; OMIM: 217700

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000245662	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine - CSER-MedSeq	criteria provided, single submitter (LMM Criteria)	Pathogenic (Aug 29, 2014)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 18474783, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000245662

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine - CSER-MedSeq

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Aug 29, 2014)

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	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification of mutations in the SLC4A11 gene in patients with recessive congenital hereditary endothelial dystrophy.

Hemadevi B, Veitia RA, Srinivasan M, Arunkumar J, Prajna NV, Lesaffre C, Sundaresan P.

Arch Ophthalmol. 2008 May;126(5):700-8. doi: 10.1001/archopht.126.5.700.

PubMed [citation]

PMID:: 18474783

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine - CSER-MedSeq, SCV000245662.1

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

Description

The Arg185ProfsX4 variant in SLC4A11 has been reported as homozygous in 1 individual with corneal endothelial dystrophy 2 (Hemadevi 2008, described as Arg158ProfsX3). Data from large population studies is insufficient to assess the frequency of this variant. This frameshift variant is predicted to alter the protein’s amino acid sequence beginning at position 185 and lead to a premature termination codon 4 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. To date, several loss-of-function variants in SLC4A11 have been associated with corneal endothelial dystrophy 2. In summary, this variant meets our criteria to be classified as pathogenic for autosomal recessive corneal endothelial dystrophy (http://personalizedmedicine.partners.org/Laboratory-For-Molecular-Medicine/).

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

Last Updated: Jun 23, 2024

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