NC_000009.12:g.(?_137139467)_(137834973_?)del AND Kleefstra syndrome 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 30, 2019
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:: RCV001031572.1

Allele description [Variation Report for NC_000009.12:g.(?_137139467)_(137834973_?)del]

NC_000009.12:g.(?_137139467)_(137834973_?)del

Genes:

NDOR1:NADPH dependent diflavin oxidoreductase 1 [Gene - OMIM - HGNC]
NOXA1:NADPH oxidase activator 1 [Gene - OMIM - HGNC]
NSMF:NMDA receptor synaptonuclear signaling and neuronal migration factor [Gene - OMIM - HGNC]
NRARP:NOTCH regulated ankyrin repeat protein [Gene - OMIM - HGNC]
SSNA1:SS nuclear autoantigen 1 [Gene - OMIM - HGNC]
ANAPC2:anaphase promoting complex subunit 2 [Gene - OMIM - HGNC]
ARRDC1:arrestin domain containing 1 [Gene - OMIM - HGNC]
CIMIP2A:ciliary microtubule inner protein 2A [Gene - HGNC]
CYSRT1:cysteine rich tail 1 [Gene - HGNC]
DPH7:diphthamide biosynthesis 7 [Gene - OMIM - HGNC]
ENTPD8:ectonucleoside triphosphate diphosphohydrolase 8 [Gene - OMIM - HGNC]
EHMT1:euchromatic histone lysine methyltransferase 1 [Gene - OMIM - HGNC]
EXD3:exonuclease 3'-5' domain containing 3 [Gene - HGNC]
GRIN1:glutamate ionotropic receptor NMDA type subunit 1 [Gene - OMIM - HGNC]
LRRC26:leucine rich repeat containing 26 [Gene - OMIM - HGNC]
MRPL41:mitochondrial ribosomal protein L41 [Gene - OMIM - HGNC]
NELFB:negative elongation factor complex member B [Gene - OMIM - HGNC]
PNPLA7:patatin like phospholipase domain containing 7 [Gene - OMIM - HGNC]
RNF208:ring finger protein 208 [Gene - OMIM - HGNC]
RNF224:ring finger protein 224 [Gene - HGNC]
SLC34A3:solute carrier family 34 member 3 [Gene - OMIM - HGNC]
STPG3:sperm-tail PG-rich repeat containing 3 [Gene - HGNC]
TPRN:taperin [Gene - OMIM - HGNC]
TOR4A:torsin family 4 member A [Gene - HGNC]
TMEM203:transmembrane protein 203 [Gene - OMIM - HGNC]
TMEM210:transmembrane protein 210 [Gene - HGNC]
TUBB4B:tubulin beta 4B class IVb [Gene - OMIM - HGNC]
LOC651337:uncharacterized LOC651337 [Gene]
ZMYND19:zinc finger MYND-type containing 19 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

9q34.3

Genomic location:

Chr9: 140033919 - 140729425 (on Assembly GRCh37)

Preferred name:

NC_000009.12:g.(?_137139467)_(137834973_?)del

HGVS:

NC_000009.12:g.(?_137139467)_(137834973_?)del
NC_000009.11:g.(?_140033919)_(140729425_?)del

Condition(s)

Name:: Kleefstra syndrome 1
Identifiers:: MONDO: MONDO:0027407; MedGen: C0795833; Orphanet: 261494; OMIM: 610253

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001194878	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 30, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26833960, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001194878

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 30, 2019)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Expanding the phenotypic profile of Kleefstra syndrome: A female with low-average intelligence and childhood apraxia of speech.

Samango-Sprouse C, Lawson P, Sprouse C, Stapleton E, Sadeghin T, Gropman A.

Am J Med Genet A. 2016 May;170A(5):1312-6. doi: 10.1002/ajmg.a.37575. Epub 2016 Feb 1.

PubMed [citation]

PMID:: 26833960

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001194878.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

A gross deletion of the genomic region encompassing the full coding sequence of the EHMT1 gene has been identified. The boundaries of this event are unknown as the deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. A similar copy number variant has been observed in an individual affected with Kleefstra syndrome (PMID: 26833960). Loss-of-function variants in EHMT1 are known to be pathogenic (PMID: 16826528, 19264732). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Jul 29, 2023

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