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NM_170606.3(KMT2C):c.3863G>A (p.Arg1288Gln) AND Kleefstra syndrome 2

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 16, 2023
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:
RCV002273204.3

Allele description [Variation Report for NM_170606.3(KMT2C):c.3863G>A (p.Arg1288Gln)]

NM_170606.3(KMT2C):c.3863G>A (p.Arg1288Gln)

Gene:
KMT2C:lysine methyltransferase 2C [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q36.1
Genomic location:
Preferred name:
NM_170606.3(KMT2C):c.3863G>A (p.Arg1288Gln)
HGVS:
  • NC_000007.14:g.152205204C>T
  • NG_033948.1:g.235802G>A
  • NM_170606.3:c.3863G>AMANE SELECT
  • NP_733751.2:p.Arg1288Gln
  • NC_000007.13:g.151902289C>T
  • NM_170606.2:c.3863G>A
Protein change:
R1288Q
Links:
dbSNP: rs1345303559
NCBI 1000 Genomes Browser:
rs1345303559
Molecular consequence:
  • NM_170606.3:c.3863G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Kleefstra syndrome 2 (KLEFS2)
Identifiers:
MONDO: MONDO:0054701; MedGen: C4540395; OMIM: 617768

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002557921Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Jul 16, 2023) 		germlineclinical testing

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

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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 Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002557921.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3C. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Kleefstra syndrome 2 (MIM#617768). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to glutamine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v3: 1 heterozygote, 0 homozygotes). (I) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0904 - Non-segregation of this variant with the phenotype under investigation has been clearly demonstrated. This variant has been shown to be inherited from an unaffected parent. (SB) 1007 - No published functional evidence has been identified for this variant. (I) 1205 - This variant has been shown to be maternally inherited. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 29, 2024