Submissions for variant NM_001374353.1(GLI2):c.4281G>A (p.Met1427Ile)

gnomAD frequency: 0.00465  dbSNP: rs146467786

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000174551	SCV000225869	benign	not specified	2014-07-10	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000314146	SCV000416234	likely benign	Holoprosencephaly 9	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000438650	SCV000510892	benign	not provided	2016-10-13	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000438650	SCV000883948	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081349	SCV001107074	benign	Holoprosencephaly 9; Postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome	2019-12-31	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000314146	SCV001435212	benign	Holoprosencephaly 9		criteria provided, single submitter	research	The heterozygous p.Met1444Ile variant, sometimes called p.Met1116Ile due to a difference in cDNA numbering, in GLI2 has been identified in an individual with possible holoprosencephaly and 4 individuals with combined pituitary hormone deficiency but not holoprosencephaly (PMID: 17096318, 22967285). This variant has also been identified in >6% of Latino chromosomes and 20 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for autosomal dominant holoprosencephaly with heminasal aplasia and orbital anomalies.
GeneDx	RCV000438650	SCV001889037	benign	not provided	2018-11-06	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27535533, 17096318, 22967285)
Fulgent Genetics, Fulgent Genetics	RCV001081349	SCV002807058	benign	Holoprosencephaly 9; Postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome	2021-12-09	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000438650	SCV004149122	benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	GLI2: BP4, BS1, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV000438650	SCV005262756	likely benign	not provided		criteria provided, single submitter	not provided