NC_000007.14:g.152052676_152295696del AND Kleefstra syndrome 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 13, 2021
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:: RCV001839258.1

Allele description [Variation Report for NC_000007.14:g.152052676_152295696del]

NC_000007.14:g.152052676_152295696del

Genes:

LOC129999675:ATAC-STARR-seq lymphoblastoid active region 26876 [Gene]
LOC126860227:BRD4-independent group 4 enhancer GRCh37_chr7:151804574-151805773 [Gene]
LOC129389938:MPRA-validated peak6855 silencer [Gene]
LOC123956272:Sharpr-MPRA regulatory region 15588 [Gene]
KMT2C:lysine methyltransferase 2C [Gene - OMIM - HGNC]
GALNT11:polypeptide N-acetylgalactosaminyltransferase 11 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

7q36.1

Genomic location:

Chr7: 152052676 - 152295696 (on Assembly GRCh38)

Preferred name:

NC_000007.14:g.152052676_152295696del

HGVS:

NC_000007.14:g.152052676_152295696del

Observations:

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002099230	New York Genome Center - CSER-NYCKidSeq	criteria provided, single submitter (NYGC Assertion Criteria 2020)	Pathogenic (Apr 13, 2021)	de novo	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002099230

New York Genome Center - CSER-NYCKidSeq

criteria provided, single submitter

(NYGC Assertion Criteria 2020)

Pathogenic
(Apr 13, 2021)

de novo

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	de novo	unknown	1	not provided	not provided	1	not provided	clinical testing

Details of each submission

From New York Genome Center - CSER-NYCKidSeq, SCV002099230.2

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

Description

The de novo ~243kb deletion deletes the last 53 exons (exon 7-59) of the KMT2C gene. The majority of pathogenic variants in KMT2C are nonsense or frameshift [PMID: 29069077; PMID: 32366967], suggesting loss-of-function is the likely mechanism of the disease. ClinGen Dosage Sensitivity curation [https://search.clinicalgenome.org/kb/gene-dosage/HGNC:13726] indicates that the KMT2C gene has a haploinsufficiency score of 3 (i.e.,sufficient evidence for haploinsufficiency). Based on the available evidence, this de novo ~243kb deletion is classified as pathogenic.

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

Last Updated: Oct 14, 2023

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