NM_001374353.1(GLI2):c.1393A>T (p.Lys465Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 6, 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:: RCV002877282.3

Allele description [Variation Report for NM_001374353.1(GLI2):c.1393A>T (p.Lys465Ter)]

NM_001374353.1(GLI2):c.1393A>T (p.Lys465Ter)

Gene:

GLI2:GLI family zinc finger 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q14.2

Genomic location:

Preferred name:

NM_001374353.1(GLI2):c.1393A>T (p.Lys465Ter)

HGVS:

NC_000002.12:g.120978509A>T
NG_009030.1:g.186219A>T
NG_009030.2:g.247643A>T
NM_001371271.1:c.1444A>T
NM_001374353.1:c.1393A>TMANE SELECT
NM_001374354.1:c.1018A>T
NM_005270.5:c.1444A>T
NP_001358200.1:p.Lys482Ter
NP_001361282.1:p.Lys465Ter
NP_001361283.1:p.Lys340Ter
NP_005261.2:p.Lys482Ter
NC_000002.11:g.121736085A>T

Protein change:

K340*

Molecular consequence:

NM_001371271.1:c.1444A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001374353.1:c.1393A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001374354.1:c.1018A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_005270.5:c.1444A>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Holoprosencephaly 9 (HPE9)
Synonyms:: PITUITARY ANOMALIES WITH HOLOPROSENCEPHALY-LIKE FEATURES; HOLOPROSENCEPHALY WITH MICROPHTHALMIA AND FIRST BRANCHIAL ARCH ANOMALIES
Identifiers:: MONDO: MONDO:0012563; MedGen: C1835819; Orphanet: 2162; OMIM: 610829

Name:: Postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome
Synonyms:: Culler-Jones syndrome
Identifiers:: MONDO: MONDO:0014369; MedGen: C4014479; Orphanet: 420584; OMIM: 615849

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003241376	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 6, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20685856, 24744436, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003241376

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 6, 2021)

germline

clinical testing

PubMed (3)
[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

Novel heterozygous nonsense GLI2 mutations in patients with hypopituitarism and ectopic posterior pituitary lobe without holoprosencephaly.

França MM, Jorge AA, Carvalho LR, Costalonga EF, Vasques GA, Leite CC, Mendonca BB, Arnhold IJ.

J Clin Endocrinol Metab. 2010 Nov;95(11):E384-91. doi: 10.1210/jc.2010-1050. Epub 2010 Aug 4.

PubMed [citation]

PMID:: 20685856

Pathogenic mutations in GLI2 cause a specific phenotype that is distinct from holoprosencephaly.

Bear KA, Solomon BD, Antonini S, Arnhold IJ, França MM, Gerkes EH, Grange DK, Hadley DW, Jääskeläinen J, Paulo SS, Rump P, Stratakis CA, Thompson EM, Willis M, Winder TL, Jorge AA, Roessler E, Muenke M.

J Med Genet. 2014 Jun;51(6):413-8. doi: 10.1136/jmedgenet-2013-102249. Epub 2014 Apr 17.

PubMed [citation]

PMID:: 24744436
PMCID:: PMC6417429

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003241376.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Lys482*) in the GLI2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GLI2 are known to be pathogenic (PMID: 20685856, 24744436). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GLI2-related conditions. For these reasons, this variant has been classified as Pathogenic.

#	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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