NM_007035.4(KERA):c.739A>G (p.Asn247Asp) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 5, 2023
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:: RCV003851946.2

Allele description [Variation Report for NM_007035.4(KERA):c.739A>G (p.Asn247Asp)]

NM_007035.4(KERA):c.739A>G (p.Asn247Asp)

Gene:

KERA:keratocan [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q21.33

Genomic location:

Preferred name:

NM_007035.4(KERA):c.739A>G (p.Asn247Asp)

HGVS:

NC_000012.12:g.91055543T>C
NG_021223.1:g.7812A>G
NM_007035.4:c.739A>GMANE SELECT
NP_008966.1:p.Asn247Asp
NP_008966.1:p.Asn247Asp
LRG_538t1:c.739A>G
LRG_538:g.7812A>G
LRG_538p1:p.Asn247Asp
NC_000012.11:g.91449320T>C
NM_007035.3:c.739A>G

Protein change:

N247D

Molecular consequence:

NM_007035.4:c.739A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004659823	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 5, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10802664, 17679937, 28677912, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004659823

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 5, 2023)

germline

clinical testing

PubMed (4)
[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

Mutations in KERA, encoding keratocan, cause cornea plana.

Pellegata NS, Dieguez-Lucena JL, Joensuu T, Lau S, Montgomery KT, Krahe R, Kivelä T, Kucherlapati R, Forsius H, de la Chapelle A.

Nat Genet. 2000 May;25(1):91-5.

PubMed [citation]

PMID:: 10802664

Study of p.N247S KERA mutation in a British family with cornea plana.

Liskova P, Hysi PG, Williams D, Ainsworth JR, Shah S, de la Chapelle A, Tuft SJ, Bhattacharya SS.

Mol Vis. 2007 Jul 27;13:1339-47.

PubMed [citation]

PMID:: 17679937

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004659823.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 247 of the KERA protein (p.Asn247Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KERA-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant disrupts the p.Asn247 amino acid residue in KERA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10802664, 17679937, 28677912). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Sep 29, 2024

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