NM_013275.6(ANKRD11):c.2408_2412del (p.Lys803fs) AND KBG syndrome

Germline classification:: Pathogenic (9 submissions)
Last evaluated:: Jul 23, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000256444.18

Allele description [Variation Report for NM_013275.6(ANKRD11):c.2408_2412del (p.Lys803fs)]

NM_013275.6(ANKRD11):c.2408_2412del (p.Lys803fs)

Gene:

ANKRD11:ankyrin repeat domain containing 11 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

16q24.3

Genomic location:

Preferred name:

NM_013275.6(ANKRD11):c.2408_2412del (p.Lys803fs)

HGVS:

NC_000016.10:g.89284131_89284135del
NG_032003.2:g.211428_211432del
NM_001256182.2:c.2408_2412del
NM_001256183.2:c.2408_2412del
NM_013275.6:c.2408_2412delMANE SELECT
NP_001243111.1:p.Lys803fs
NP_001243112.1:p.Lys803fs
NP_037407.4:p.Lys803fs
NC_000016.9:g.89350538_89350542del
NC_000016.9:g.89350539_89350543del
NG_032003.1:g.211428_211432del
NM_001256182.1:c.2408_2412del
NM_001256182.2:c.2408_2412delAAAAA
NM_013275.4:c.2408_2412delAAAAA
NM_013275.5:c.2408_2412del
NM_013275.5:c.2408_2412del5
NM_013275.5:c.2408_2412delAAAAA
NM_013275.6:c.2408_2412delAAAAAMANE SELECT

Protein change:

K803fs

Links:

dbSNP: rs886039902

NCBI 1000 Genomes Browser:

rs886039902

Molecular consequence:

NM_001256182.2:c.2408_2412del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001256183.2:c.2408_2412del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_013275.6:c.2408_2412del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: KBG syndrome (KBGS)
Synonyms:: Short stature, characteristic facies, macrodontia, mental retardation, and skeletal anomalies
Identifiers:: MONDO: MONDO:0007846; MedGen: C0220687; Orphanet: 2332; OMIM: 148050

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000323203	HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - CSER-HudsonAlpha	criteria provided, single submitter (HA_assertions_20161101)	Pathogenic (Sep 15, 2016)	unknown	research	Citation Link,
SCV000823257	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 23, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 27667800, 21782149, 25125236, 25413698, 25652421, 28492532
SCV000966193	Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 9, 2018)	maternal	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001429227	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 9, 2020)	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001438088	Autoinflammatory diseases unit, CHU de Montpellier	no assertion criteria provided	Pathogenic (Apr 15, 2016)	de novo	clinical testing
SCV001443557	GenomeConnect - Simons Searchlight	no assertion criteria provided	Pathogenic (Sep 10, 2018)	unknown	provider interpretation
SCV002097344	Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 1, 2021)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV002784845	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 6, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003836673	Laboratoire de Génétique Moléculaire, CHU Bordeaux	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 28, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	de novo	yes	3	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing, research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	maternal	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	yes	1	not provided	not provided	1	not provided	research, provider interpretation
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical and genetic aspects of KBG syndrome.

Low K, Ashraf T, Canham N, Clayton-Smith J, Deshpande C, Donaldson A, Fisher R, Flinter F, Foulds N, Fryer A, Gibson K, Hayes I, Hills A, Holder S, Irving M, Joss S, Kivuva E, Lachlan K, Magee A, McConnell V, McEntagart M, Metcalfe K, et al.

Am J Med Genet A. 2016 Nov;170(11):2835-2846. doi: 10.1002/ajmg.a.37842. Epub 2016 Sep 26.

PubMed [citation]

PMID:: 27667800
PMCID:: PMC5435101

Mutations in ANKRD11 cause KBG syndrome, characterized by intellectual disability, skeletal malformations, and macrodontia.

Sirmaci A, Spiliopoulos M, Brancati F, Powell E, Duman D, Abrams A, Bademci G, Agolini E, Guo S, Konuk B, Kavaz A, Blanton S, Digilio MC, Dallapiccola B, Young J, Zuchner S, Tekin M.

Am J Hum Genet. 2011 Aug 12;89(2):289-94. doi: 10.1016/j.ajhg.2011.06.007. Epub 2011 Jul 21.

PubMed [citation]

PMID:: 21782149
PMCID:: PMC3155157

See all PubMed Citations (7)

Details of each submission

From HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - CSER-HudsonAlpha, SCV000323203.4

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

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000823257.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This premature translational stop signal has been observed in individuals with KBG syndrome (PMID: 27667800). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 266033). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys803Argfs*5) in the ANKRD11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ANKRD11 are known to be pathogenic (PMID: 21782149, 25125236, 25413698, 25652421).

#	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

From Equipe Genetique des Anomalies du Developpement, Université de Bourgogne, SCV000966193.1

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

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

From Institute of Human Genetics, University of Leipzig Medical Center, SCV001429227.1

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

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

From Autoinflammatory diseases unit, CHU de Montpellier, SCV001438088.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	not provided	not provided	not provided		2	not provided	not provided	not provided

From GenomeConnect - Simons Searchlight, SCV001443557.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	provider interpretation	not provided

Description

Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-09-10 and interpreted as Pathogenic. Variant was initially reported on 2018-01-09 by GTR ID of laboratory name 506154. The reporting laboratory might also submit to ClinVar.

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

From Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano, SCV002097344.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	research	PubMed (1)

#	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		1	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV002784845.1

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

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

From Laboratoire de Génétique Moléculaire, CHU Bordeaux, SCV003836673.1

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

#	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: Dec 22, 2024

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