Submissions for variant NM_170675.5(MEIS2):c.934_937del (p.Leu312fs)

dbSNP: rs1595790647

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Mendelics	RCV000989283	SCV001139541	likely pathogenic	Cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies	2019-05-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001265871	SCV001444043	pathogenic	Inborn genetic diseases	2024-03-01	criteria provided, single submitter	clinical testing	The c.934_937delTTAG (p.L312Rfs*11) alteration, located in coding exon 9 of the MEIS2 gene, consists of a deletion of 4 nucleotides from position 934 to 937, causing a translational frameshift with a predicted alternate stop codon after 11 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant was reported in multiple individuals with features consistent with MEIS2-related neurodevelopmental disorder, including two de novo occurrences (Verheije, 2019; Hildebrand, 2020; Ambry internal data). Based on the available evidence, this alteration is classified as pathogenic.
Laboratory of Medical Genetics, National & Kapodistrian University of Athens	RCV000989283	SCV001976846	pathogenic	Cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies	2021-10-05	criteria provided, single submitter	clinical testing	PVS1, PM2, PP5
GeneDx	RCV005054285	SCV005688000	pathogenic	not provided	2024-08-03	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 33722742, 32345733, 30291340)
Génétique des Maladies du Développement, Hospices Civils de Lyon	RCV000989283	SCV001712275	pathogenic	Cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies		no assertion criteria provided	clinical testing
OMIM	RCV000989283	SCV002320687	pathogenic	Cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies	2022-12-19	no assertion criteria provided	literature only
Department of Rehabilitation Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea	RCV000989283	SCV004697956	pathogenic	Cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies		no assertion criteria provided	clinical testing