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NM_000168.6(GLI3):c.602_675del (p.Met201fs) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 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:
RCV001894291.4

Allele description [Variation Report for NM_000168.6(GLI3):c.602_675del (p.Met201fs)]

NM_000168.6(GLI3):c.602_675del (p.Met201fs)

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.602_675del (p.Met201fs)
HGVS:
  • NC_000007.14:g.42048502_42048575del
  • NG_008434.1:g.193452_193525del
  • NM_000168.6:c.602_675delMANE SELECT
  • NP_000159.3:p.Met201fs
  • NC_000007.13:g.42088094_42088167del
  • NC_000007.13:g.42088101_42088174del
Protein change:
M201fs
Links:
dbSNP: rs2128742642
NCBI 1000 Genomes Browser:
rs2128742642
Molecular consequence:
  • NM_000168.6:c.602_675del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Greig cephalopolysyndactyly syndrome (GCPS)
Synonyms:
Greig syndrome; Polysyndactyly with peculiar skull shape
Identifiers:
MONDO: MONDO:0008287; MedGen: C0265306; Orphanet: 380; OMIM: 175700
Name:
Pallister-Hall syndrome (PHS)
Synonyms:
Hypothalamic hamartoblastoma, hypopituitarism, imperforate anus, and postaxial polydactyly
Identifiers:
MONDO: MONDO:0007804; MedGen: C0265220; Orphanet: 672; OMIM: 146510

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002122784Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Nov 6, 2021) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

The phenotypic spectrum of GLI3 morphopathies includes autosomal dominant preaxial polydactyly type-IV and postaxial polydactyly type-A/B; No phenotype prediction from the position of GLI3 mutations.

Radhakrishna U, Bornholdt D, Scott HS, Patel UC, Rossier C, Engel H, Bottani A, Chandal D, Blouin JL, Solanki JV, Grzeschik KH, Antonarakis SE.

Am J Hum Genet. 1999 Sep;65(3):645-55.

PubMed [citation]
PMID:
10441570
PMCID:
PMC1377970

Molecular and clinical analyses of Greig cephalopolysyndactyly and Pallister-Hall syndromes: robust phenotype prediction from the type and position of GLI3 mutations.

Johnston JJ, Olivos-Glander I, Killoran C, Elson E, Turner JT, Peters KF, Abbott MH, Aughton DJ, Aylsworth AS, Bamshad MJ, Booth C, Curry CJ, David A, Dinulos MB, Flannery DB, Fox MA, Graham JM, Grange DK, Guttmacher AE, Hannibal MC, Henn W, Hennekam RC, et al.

Am J Hum Genet. 2005 Apr;76(4):609-22. Epub 2005 Feb 28.

PubMed [citation]
PMID:
15739154
PMCID:
PMC1199298
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002122784.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Met201Argfs*51) in the GLI3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GLI3 are known to be pathogenic (PMID: 10441570, 15739154, 18000979, 24736735). This variant has not been reported in the literature in individuals affected with GLI3-related conditions. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024