NM_013275.6(ANKRD11):c.2716C>T (p.Arg906Ter) AND KBG syndrome

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Dec 13, 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:: RCV000995491.6

Allele description [Variation Report for NM_013275.6(ANKRD11):c.2716C>T (p.Arg906Ter)]

NM_013275.6(ANKRD11):c.2716C>T (p.Arg906Ter)

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.2716C>T (p.Arg906Ter)

HGVS:

NC_000016.10:g.89283826G>A
NG_032003.2:g.211736C>T
NM_001256182.2:c.2716C>T
NM_001256183.2:c.2716C>T
NM_013275.6:c.2716C>TMANE SELECT
NP_001243111.1:p.Arg906Ter
NP_001243112.1:p.Arg906Ter
NP_037407.4:p.Arg906Ter
NC_000016.9:g.89350234G>A
NC_000016.9:g.89350234G>A
NG_032003.1:g.211736C>T

Protein change:

R906*

Links:

dbSNP: rs929007085

NCBI 1000 Genomes Browser:

rs929007085

Molecular consequence:

NM_001256182.2:c.2716C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001256183.2:c.2716C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_013275.6:c.2716C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV001149679	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	criteria provided, single submitter (Classification criteria August 2017)	Pathogenic (Aug 16, 2019)	de novo	clinical testing	Citation Link,
SCV002574806	Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin See additional submitters CUBI - Core Unit Bioinformatics, Berlin Institute of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 22, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004296429	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 13, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 21782149, 25125236, 25413698, 25652421, 26633542, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001149679

Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München

criteria provided, single submitter

(Classification criteria August 2017)

Pathogenic
(Aug 16, 2019)

de novo

clinical testing

Citation Link,

SCV002574806

Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 22, 2022)

germline

clinical testing

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

SCV004296429

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 13, 2023)

germline

clinical testing

PubMed (6)
[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	de novo	yes	1	not provided	not provided	1	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	1	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

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 Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München, SCV001149679.1

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

From Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, SCV002574806.1

#	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	germline	yes	1	Blood	not provided		1	not provided	not provided	not provided

From Invitae, SCV004296429.1

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

Description

This sequence change creates a premature translational stop signal (p.Arg906*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with ANKRD11-related conditions (PMID: 26633542). ClinVar contains an entry for this variant (Variation ID: 807371). 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: Apr 20, 2024

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