ClinVar Genomic variation as it relates to human health
NM_170675.5(MEIS2):c.934_937del (p.Leu312fs)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_170675.5(MEIS2):c.934_937del (p.Leu312fs)
Variation ID: 803063 Accession: VCV000803063.8
- Type and length
-
Deletion, 4 bp
- Location
-
Cytogenetic: 15q14 15: 36950364-36950367 (GRCh38) [ NCBI UCSC ] 15: 37242565-37242568 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jan 11, 2020 Mar 10, 2024 Oct 5, 2021 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_170675.5:c.934_937del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_733775.1:p.Leu312fs frameshift NM_001220482.2:c.934_937del NP_001207411.1:p.Leu312fs frameshift NM_002399.4:c.895_898del NP_002390.1:p.Leu299fs frameshift NM_170674.5:c.934_937del NP_733774.1:p.Leu312fs frameshift NM_170676.5:c.934_937del NP_733776.1:p.Leu312fs frameshift NM_170677.5:c.934_937del NP_733777.1:p.Leu312fs frameshift NM_172315.3:c.895_898del NP_758526.1:p.Leu299fs frameshift NM_172316.3:c.670_673del NP_758527.1:p.Leu224fs frameshift NC_000015.10:g.36950366_36950369del NC_000015.9:g.37242567_37242570del NG_029108.1:g.155933_155936del NG_053466.1:g.1863_1866del - Protein change
- L224fs, L299fs, L312fs
- Other names
- -
- Canonical SPDI
- NC_000015.10:36950363:CTAACT:CT
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
MEIS2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
136 | 158 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Oct 5, 2021 | RCV000989283.6 | |
Pathogenic (1) |
criteria provided, single submitter
|
Oct 23, 2018 | RCV001265871.2 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Likely pathogenic
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001139541.1
First in ClinVar: Jan 11, 2020 Last updated: Jan 11, 2020 |
|
|
Pathogenic
(Oct 05, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies
Affected status: yes
Allele origin:
unknown
|
Laboratory of Medical Genetics, National & Kapodistrian University of Athens
Accession: SCV001976846.1
First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
Comment:
PVS1, PM2, PP5
|
|
Pathogenic
(Oct 23, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: yes
Allele origin:
germline
|
Ambry Genetics
Accession: SCV001444043.2
First in ClinVar: Nov 21, 2020 Last updated: Jan 07, 2023 |
Observation 1:
Number of individuals with the variant: 1
Sex: male
Ethnicity/Population group: Caucasian
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
Autistic behavior (present) , Feeding difficulties (present) , Narrow mouth (present) , Muscular hypotonia (present) , Behavioral abnormality (present) , Hearing impairment (present) , Global … (more)
Autistic behavior (present) , Feeding difficulties (present) , Narrow mouth (present) , Muscular hypotonia (present) , Behavioral abnormality (present) , Hearing impairment (present) , Global developmental delay (present) (less)
Sex: female
Ethnicity/Population group: Caucasian
Observation 3:
Number of individuals with the variant: 1
Clinical Features:
Neurodevelopmental delay (present) , Autistic disorder of childhood onset (present) , Seizures (present) , Behavioral abnormality (present) , Gait disturbance (present) , Eczema (present) , … (more)
Neurodevelopmental delay (present) , Autistic disorder of childhood onset (present) , Seizures (present) , Behavioral abnormality (present) , Gait disturbance (present) , Eczema (present) , Cleft uvula (present) , Truncal ataxia (present) , Delayed speech and language development (present) , Motor delay (present) (less)
Sex: female
Ethnicity/Population group: Indian
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
|
Génétique des Maladies du Développement, Hospices Civils de Lyon
Accession: SCV001712275.1
First in ClinVar: Jun 15, 2021 Last updated: Jun 15, 2021 |
Sex: male
|
|
Pathogenic
(Dec 19, 2022)
|
no assertion criteria provided
Method: literature only
|
CLEFT PALATE, CARDIAC DEFECTS, AND IMPAIRED INTELLECTUAL DEVELOPMENT
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV002320687.2
First in ClinVar: Apr 07, 2022 Last updated: Dec 24, 2022 |
Comment on evidence:
By targeted sequencing of the MEIS2 gene in an 11-year-old girl (patient 8) with cleft palate, cardiac defects, and impaired intellectual development (CPCMR; 600987), Verheije … (more)
By targeted sequencing of the MEIS2 gene in an 11-year-old girl (patient 8) with cleft palate, cardiac defects, and impaired intellectual development (CPCMR; 600987), Verheije et al. (2019) identified a 4-bp deletion (c.934_937del, NM_170674.4) that resulted in a frameshift and a premature stop codon (Leu312argfsTer11). (less)
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies
Affected status: yes
Allele origin:
unknown
|
Department of Rehabilitation Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea
Accession: SCV004697956.1
First in ClinVar: Mar 10, 2024 Last updated: Mar 10, 2024 |
|
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Heterozygous loss-of-function variants of MEIS2 cause a triad of palatal defects, congenital heart defects, and intellectual disability. | Verheije R | European journal of human genetics : EJHG | 2019 | PMID: 30291340 |
Text-mined citations for rs1595790647 ...
HelpRecord last updated Mar 11, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.