NM_000168.6(GLI3):c.4445del (p.Pro1482fs) AND Greig cephalopolysyndactyly syndrome

Germline classification:: Likely pathogenic (1 submission)
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:: RCV004557280.2

Allele description [Variation Report for NM_000168.6(GLI3):c.4445del (p.Pro1482fs)]

NM_000168.6(GLI3):c.4445del (p.Pro1482fs)

Gene:

GLI3:GLI family zinc finger 3 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

7p14.1

Genomic location:

Preferred name:

NM_000168.6(GLI3):c.4445del (p.Pro1482fs)

HGVS:

NC_000007.14:g.41964631del
NG_008434.1:g.277393del
NG_008434.2:g.304640del
NM_000168.6:c.4445delMANE SELECT
NP_000159.3:p.Pro1482fs
NC_000007.13:g.42004229del
NM_000168.6:c.4445delCMANE SELECT

Protein change:

P1482fs

Links:

dbSNP: rs2484363262

NCBI 1000 Genomes Browser:

rs2484363262

Molecular consequence:

NM_000168.6:c.4445del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Greig cephalopolysyndactyly syndrome (GCPS)
Synonyms:: POLYSYNDACTYLY WITH PECULIAR SKULL SHAPE; Greig syndrome
Identifiers:: MONDO: MONDO:0008287; MedGen: C0265306; Orphanet: 380; OMIM: 175700

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005046461	HUSP Clinical Genetics Laboratory, Hospital Universitario San Pedro De Logroño (HUSP)	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	paternal	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005046461

HUSP Clinical Genetics Laboratory, Hospital Universitario San Pedro De Logroño (HUSP)

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

paternal

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	paternal	yes	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 HUSP Clinical Genetics Laboratory, Hospital Universitario San Pedro De Logroño (HUSP), SCV005046461.1

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

Description

The variant was detected in amniotic fluid of a male fetus with macrocephaly and in his father who had no clinical features to our knowledge. They both were heterozygous for the variant c.4445delC in the exon 15 of gen GLI3 NM_000168. It results in a frameshift, a premature termination codon and, therefore, a truncated protein (p.Pro1482GlnfsTer6). This variant is not detected in general population and has not been reported in pathogenic data bases. Pathogenic variants in gen GLI3 have been associated with Grieg Syndrome with cephalopolysyndactyly (GCPS; OMIM 175700) or with Pallister-Hall Syndrome (PHS; OMIM 146510) both with autosomal dominant inheritance. According to the variant position in the gen, it is more likely to correlate with GCPS phenotype which includes macrocephaly. Unfortunally the fetus passed away shortly after being born.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	paternal	yes	not provided	not provided	not provided		2	not provided	not provided	not provided

Last Updated: May 16, 2025

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