NM_013275.6(ANKRD11):c.7535G>A (p.Arg2512Gln) AND KBG syndrome

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Oct 2, 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:: RCV001199356.3

Allele description [Variation Report for NM_013275.6(ANKRD11):c.7535G>A (p.Arg2512Gln)]

NM_013275.6(ANKRD11):c.7535G>A (p.Arg2512Gln)

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.7535G>A (p.Arg2512Gln)

HGVS:

NC_000016.10:g.89275127C>T
NG_032003.2:g.220435G>A
NM_001256182.2:c.7535G>A
NM_001256183.2:c.7535G>A
NM_013275.4:c.7535G>A
NM_013275.6:c.7535G>AMANE SELECT
NP_001243111.1:p.Arg2512Gln
NP_001243112.1:p.Arg2512Gln
NP_037407.4:p.Arg2512Gln
NC_000016.9:g.89341535C>T
NG_032003.1:g.220435G>A
NM_001256182.1:c.7535G>A
NM_013275.5:c.7535G>A

Protein change:

R2512Q

Links:

dbSNP: rs2033535934

NCBI 1000 Genomes Browser:

rs2033535934

Molecular consequence:

NM_001256182.2:c.7535G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001256183.2:c.7535G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_013275.6:c.7535G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001370455	Centre for Mendelian Genomics, University Medical Centre Ljubljana	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 23, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002012212	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 2, 2021)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25413698, 26633542, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001370455

Centre for Mendelian Genomics, University Medical Centre Ljubljana

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 23, 2019)

unknown

clinical testing

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

SCV002012212

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 2, 2021)

unknown

clinical testing

PubMed (3)
[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	unknown	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Characterization of ANKRD11 mutations in humans and mice related to KBG syndrome.

Walz K, Cohen D, Neilsen PM, Foster J 2nd, Brancati F, Demir K, Fisher R, Moffat M, Verbeek NE, Bjørgo K, Lo Castro A, Curatolo P, Novelli G, Abad C, Lei C, Zhang L, Diaz-Horta O, Young JI, Callen DF, Tekin M.

Hum Genet. 2015 Feb;134(2):181-90. doi: 10.1007/s00439-014-1509-2. Epub 2014 Nov 21.

PubMed [citation]

PMID:: 25413698

Clinical application of whole-exome sequencing across clinical indications.

Retterer K, Juusola J, Cho MT, Vitazka P, Millan F, Gibellini F, Vertino-Bell A, Smaoui N, Neidich J, Monaghan KG, McKnight D, Bai R, Suchy S, Friedman B, Tahiliani J, Pineda-Alvarez D, Richard G, Brandt T, Haverfield E, Chung WK, Bale S.

Genet Med. 2016 Jul;18(7):696-704. doi: 10.1038/gim.2015.148. Epub 2015 Dec 3.

PubMed [citation]

PMID:: 26633542

See all PubMed Citations (3)

Details of each submission

From Centre for Mendelian Genomics, University Medical Centre Ljubljana, SCV001370455.2

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

Description

This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PM1,PM2,PP3,PP5.

#	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 3billion, SCV002012212.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (3)

Description

Same nucleotide change resulting in same amino acid change has been previously reported as de novoo in similarly affected unrelated individuals (PMID: 25413698, PS2, PS4_M). It is not observed in the gnomAD v2.1.1 dataset (PM2). A different missense change at the same codon (p.Arg2512Trp) has been reported as pathogenic (PMID: 25413698, PM5). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.834, 3Cnet: 0.888, PP3). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

#	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

Last Updated: Jun 23, 2024

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