NM_170675.5(MEIS2):c.992GAA[2] (p.Arg333del) AND Cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Nov 29, 2022
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:: RCV000210625.7

Allele description [Variation Report for NM_170675.5(MEIS2):c.992GAA[2] (p.Arg333del)]

NM_170675.5(MEIS2):c.992GAA[2] (p.Arg333del)

Gene:

MEIS2:Meis homeobox 2 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

15q14

Genomic location:

Preferred name:

NM_170675.5(MEIS2):c.992GAA[2] (p.Arg333del)

HGVS:

NC_000015.10:g.36896665TCT[2]
NG_029108.1:g.209628GAA[2]
NM_001220482.2:c.992GAA[2]
NM_002399.4:c.953GAA[2]
NM_170674.5:c.992GAA[2]
NM_170675.5:c.992GAA[2]MANE SELECT
NM_170676.5:c.992GAA[2]
NM_170677.5:c.992GAA[2]
NM_172315.3:c.953GAA[2]
NM_172316.3:c.728GAA[2]
NP_001207411.1:p.Arg333del
NP_002390.1:p.Arg320del
NP_733774.1:p.Arg333del
NP_733775.1:p.Arg333del
NP_733776.1:p.Arg333del
NP_733777.1:p.Arg333del
NP_758526.1:p.Arg320del
NP_758527.1:p.Arg245del
NC_000015.9:g.37188866TCT[2]
NM_170674.2:c.998_1000del
NM_170674.4:c.998_1000del
NM_170674.4:c.998_1000delGAA
NM_170675.3:c.998_1000delGAA
NM_170675.5:c.998_1000delMANE SELECT
NM_170677.4:c.998_1000delGAA
NR_051953.2:n.1998GAA[2]

Protein change:

R245del

Links:

OMIM: 601740.0001; dbSNP: rs879255264

NCBI 1000 Genomes Browser:

rs879255264

Molecular consequence:

NM_001220482.2:c.992GAA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_002399.4:c.953GAA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_170674.5:c.992GAA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_170675.5:c.992GAA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_170676.5:c.992GAA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_170677.5:c.992GAA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_172315.3:c.953GAA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_172316.3:c.728GAA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NR_051953.2:n.1998GAA[2] - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies
Synonyms:: CLEFT PALATE, CARDIAC DEFECTS, AND IMPAIRED INTELLECTUAL DEVELOPMENT
Identifiers:: MONDO: MONDO:0010970; MedGen: C1832950; OMIM: 600987

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000266813	OMIM	no assertion criteria provided	Pathogenic (Dec 19, 2022)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002760104	Laboratory of Medical Genetics, University of Torino - NeuroWES	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 29, 2022)	germline	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000266813

OMIM

no assertion criteria provided

Pathogenic
(Dec 19, 2022)

germline

literature only

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

SCV002760104

Laboratory of Medical Genetics, University of Torino - NeuroWES

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 29, 2022)

germline

research

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	germline	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

MEIS2 involvement in cardiac development, cleft palate, and intellectual disability.

Louw JJ, Corveleyn A, Jia Y, Hens G, Gewillig M, Devriendt K.

Am J Med Genet A. 2015 May;167A(5):1142-6. doi: 10.1002/ajmg.a.36989. Epub 2015 Feb 25.

PubMed [citation]

PMID:: 25712757

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 OMIM, SCV000266813.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 5-year-old girl with cleft palate, congenital heart defects, and moderate intellectual disability (CPCMR; 600987), Louw et al. (2015) identified a de novo heterozygous 3-bp in-frame deletion (c.998_1000del, NM_170674.2) in the MEIS2 gene, resulting in deletion of the highly conserved Arg333 residue in the homeodomain. The variant was found by exome sequencing and confirmed by Sanger sequencing. Functional studies and studies of patient cells were not performed, but the deletion was predicted to interfere with DNA binding and possibly to exert a dominant-negative effect rather than haploinsufficiency.

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

From Laboratory of Medical Genetics, University of Torino - NeuroWES, SCV002760104.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)

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

Last Updated: Jun 23, 2024

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