NM_013275.6(ANKRD11):c.2692C>T (p.Arg898Ter) AND KBG syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 2, 2023
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:: RCV001388447.6

Allele description [Variation Report for NM_013275.6(ANKRD11):c.2692C>T (p.Arg898Ter)]

NM_013275.6(ANKRD11):c.2692C>T (p.Arg898Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

16q24.3

Genomic location:

Preferred name:

NM_013275.6(ANKRD11):c.2692C>T (p.Arg898Ter)

HGVS:

NC_000016.10:g.89283850G>A
NG_032003.2:g.211712C>T
NM_001256182.2:c.2692C>T
NM_001256183.2:c.2692C>T
NM_013275.6:c.2692C>TMANE SELECT
NP_001243111.1:p.Arg898Ter
NP_001243112.1:p.Arg898Ter
NP_037407.4:p.Arg898Ter
NC_000016.9:g.89350258G>A
NG_032003.1:g.211712C>T
NM_013275.5:c.2692C>T

Protein change:

R898*

Links:

dbSNP: rs780011005

NCBI 1000 Genomes Browser:

rs780011005

Molecular consequence:

NM_001256182.2:c.2692C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001256183.2:c.2692C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_013275.6:c.2692C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV001589445	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 11, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 21782149, 25125236, 25413698, 25652421, 28492532
SCV003932284	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 2, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001589445

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 11, 2020)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV003932284

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 2, 2023)

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	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 (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001589445.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Arg898*) in the ANKRD11 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs780011005, ExAC 0.009%). This variant has not been reported in the literature in individuals with ANKRD11-related conditions. ClinVar contains an entry for this variant (Variation ID: 620276). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in ANKRD11 are known to be pathogenic (PMID: 21782149, 25125236, 25413698, 25652421). 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

From Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center, SCV003932284.1

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

Description

PVS1, PS2, PS4_Supporting, PM2

#	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: Oct 8, 2024

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