NM_000168.6(GLI3):c.2424A>G (p.Ile808Met) AND Greig cephalopolysyndactyly syndrome

Clinical significance:Benign/Likely benign (Last evaluated: May 28, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000365837.3

Allele description [Variation Report for NM_000168.6(GLI3):c.2424A>G (p.Ile808Met)]

NM_000168.6(GLI3):c.2424A>G (p.Ile808Met)

Gene:
GLI3:GLI family zinc finger 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p14.1
Genomic location:
Preferred name:
NM_000168.6(GLI3):c.2424A>G (p.Ile808Met)
Other names:
NM_000168.5(GLI3):c.2424A>G(p.Ile808Met)
HGVS:
  • NC_000007.14:g.41967603T>C
  • NG_008434.1:g.274418A>G
  • NM_000168.6:c.2424A>GMANE SELECT
  • NP_000159.3:p.Ile808Met
  • NC_000007.13:g.42007201T>C
  • NM_000168.5:c.2424A>G
  • P10071:p.Ile808Met
Protein change:
I808M
Links:
UniProtKB: P10071#VAR_010056; dbSNP: rs62622373
NCBI 1000 Genomes Browser:
rs62622373
Molecular consequence:
  • NM_000168.6:c.2424A>G - missense variant - [Sequence Ontology: SO:0001583]

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000469193Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Benign
(Mar 6, 2018)
germlineclinical testing

Citation Link,

SCV000803566SIB Swiss Institute of Bioinformaticscriteria provided, single submitter
Likely benign
(May 31, 2018)
unknowncuration

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

SCV001137346Mendelicscriteria provided, single submitter
Likely benign
(May 28, 2019)
unknownclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing, curation
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 Illumina Clinical Services Laboratory,Illumina, SCV000469193.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

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

From SIB Swiss Institute of Bioinformatics, SCV000803566.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)

Description

This variant is interpreted as a Likely Benign, for Greig cephalopolysyndactyly syndrome, in Autosomal Dominant manner. The following ACMG Tag(s) were applied: BS1 => Allele frequency is greater than expected for disorder. BS2-Supporting => BS2 downgraded in strength to supporting.

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

From Mendelics, SCV001137346.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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