NM_170675.5(MEIS2):c.987T>A (p.Asn329Lys) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 14, 2015
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:: RCV000494298.1

Allele description [Variation Report for NM_170675.5(MEIS2):c.987T>A (p.Asn329Lys)]

NM_170675.5(MEIS2):c.987T>A (p.Asn329Lys)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

15q14

Genomic location:

Preferred name:

NM_170675.5(MEIS2):c.987T>A (p.Asn329Lys)

HGVS:

NC_000015.10:g.36896677A>T
NG_029108.1:g.209623T>A
NM_001220482.2:c.987T>A
NM_002399.4:c.948T>A
NM_170674.5:c.987T>A
NM_170675.5:c.987T>AMANE SELECT
NM_170676.5:c.987T>A
NM_170677.5:c.987T>A
NM_172315.3:c.948T>A
NM_172316.3:c.723T>A
NP_001207411.1:p.Asn329Lys
NP_002390.1:p.Asn316Lys
NP_733774.1:p.Asn329Lys
NP_733775.1:p.Asn329Lys
NP_733776.1:p.Asn329Lys
NP_733777.1:p.Asn329Lys
NP_758526.1:p.Asn316Lys
NP_758527.1:p.Asn241Lys
NC_000015.9:g.37188878A>T
NM_170674.4:c.987T>A
NM_170677.4:c.987T>A
NR_051953.2:n.1993T>A

Protein change:

N241K

Links:

dbSNP: rs1131691404

NCBI 1000 Genomes Browser:

rs1131691404

Molecular consequence:

NM_001220482.2:c.987T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002399.4:c.948T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170674.5:c.987T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170675.5:c.987T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170676.5:c.987T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170677.5:c.987T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_172315.3:c.948T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_172316.3:c.723T>A - missense variant - [Sequence Ontology: SO:0001583]
NR_051953.2:n.1993T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: CN517202

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000582058	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Likely pathogenic (Aug 14, 2015)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000582058

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Likely pathogenic
(Aug 14, 2015)

germline

clinical testing

Citation Link

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	clinical testing

Details of each submission

From GeneDx, SCV000582058.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The N329K variant in the MEIS2 gene has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The N329K variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The N329K variant is a semi-conservative amino acid substitution, which occurs at a position within the homeobox DNA-binding domain that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. In vitro functional studies of a nearby missense variant (R332M) demonstrate impaired DNA binding and transcriptional activation (Bjerke et al., 2011), supporting the functional importance of this region of the protein. In addition, GeneDx has observed missense variants in nearby residues (R331K, V335A) in individuals referred for XomeDx analysis with clinical findings of cleft palate and global developmental delay. The N329K variant is a strong candidate for a disease-causing variant. However, the possibility it may be a rare benign variant cannot be excluded.

#	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: Apr 23, 2022

ClinVar

Relating variation to medicine