NM_013275.6(ANKRD11):c.1381_1384del (p.Glu461fs) AND KBG syndrome

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Nov 1, 2021
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:: RCV001056651.8

Allele description [Variation Report for NM_013275.6(ANKRD11):c.1381_1384del (p.Glu461fs)]

NM_013275.6(ANKRD11):c.1381_1384del (p.Glu461fs)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

16q24.3

Genomic location:

Preferred name:

NM_013275.6(ANKRD11):c.1381_1384del (p.Glu461fs)

HGVS:

NC_000016.10:g.89285158TTTC[2]
NG_032003.2:g.210393GAAA[2]
NM_001256182.2:c.1381_1384del
NM_001256183.2:c.1381_1384del
NM_013275.6:c.1381_1384delMANE SELECT
NP_001243111.1:p.Glu461fs
NP_001243112.1:p.Glu461fs
NP_037407.4:p.Glu461fs
NC_000016.9:g.89351566TTTC[2]
NC_000016.9:g.89351566_89351569del
NM_001256182.1:c.1381_1384del
NM_001256182.2:c.1381_1384delGAAA
NM_013275.4:c.1381_1384delGAAA
NM_013275.5:c.1381_1384del
NM_013275.6:c.1381_1384delGAAAMANE SELECT

Protein change:

E461fs

Links:

dbSNP: rs1597464953

NCBI 1000 Genomes Browser:

rs1597464953

Molecular consequence:

NM_001256182.2:c.1381_1384del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001256183.2:c.1381_1384del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_013275.6:c.1381_1384del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV001221104	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 7, 2019)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 21782149, 25125236, 25413698, 25652421, 27605097, 27667800, 28492532
SCV002097365	Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 1, 2021)	de novo	research	PubMed (1) [See all records that cite this PMID]
SCV003927867	Clinical Laboratory Sciences Program (CLSP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)	no assertion criteria provided	Pathogenic (Apr 1, 2023)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001221104

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 7, 2019)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

SCV002097365

Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 1, 2021)

de novo

research

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

SCV003927867

Clinical Laboratory Sciences Program (CLSP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)

no assertion criteria provided

Pathogenic
(Apr 1, 2023)

germline

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	de novo	yes	2	not provided	not provided	not provided	not provided	research
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Genetic heterogeneity in Cornelia de Lange syndrome (CdLS) and CdLS-like phenotypes with observed and predicted levels of mosaicism.

Ansari M, Poke G, Ferry Q, Williamson K, Aldridge R, Meynert AM, Bengani H, Chan CY, Kayserili H, Avci S, Hennekam RC, Lampe AK, Redeker E, Homfray T, Ross A, Falkenberg Smeland M, Mansour S, Parker MJ, Cook JA, Splitt M, Fisher RB, Fryer A, et al.

J Med Genet. 2014 Oct;51(10):659-68. doi: 10.1136/jmedgenet-2014-102573. Epub 2014 Aug 14.

PubMed [citation]

PMID:: 25125236
PMCID:: PMC4173748

See all PubMed Citations (8)

Details of each submission

From Invitae, SCV001221104.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ANKRD11 are known to be pathogenic (PMID: 21782149, 25125236, 25413698, 25652421). This variant has been observed in several individuals affected with KBG syndrome (PMID: 27605097, 27667800). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu461Glnfs*48) in the ANKRD11 gene. It is expected to result in an absent or disrupted protein product.

#	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 Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano, SCV002097365.1

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

From Clinical Laboratory Sciences Program (CLSP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), SCV003927867.1

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

Last Updated: Feb 14, 2024

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