NM_013275.6(ANKRD11):c.6797C>T (p.Ala2266Val) AND not provided

Germline classification:: Likely benign (3 submissions)
Last evaluated:: Jan 1, 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:: RCV000996393.21

Allele description [Variation Report for NM_013275.6(ANKRD11):c.6797C>T (p.Ala2266Val)]

NM_013275.6(ANKRD11):c.6797C>T (p.Ala2266Val)

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.6797C>T (p.Ala2266Val)

HGVS:

NC_000016.10:g.89279745G>A
NG_032003.2:g.215817C>T
NM_001256182.2:c.6797C>T
NM_001256183.2:c.6797C>T
NM_013275.6:c.6797C>TMANE SELECT
NP_001243111.1:p.Ala2266Val
NP_001243112.1:p.Ala2266Val
NP_037407.4:p.Ala2266Val
NC_000016.9:g.89346153G>A
NG_032003.1:g.215817C>T
NM_013275.4:c.6797C>T
NM_013275.5:c.6797C>T

Protein change:

A2266V

Links:

dbSNP: rs748996527

NCBI 1000 Genomes Browser:

rs748996527

Molecular consequence:

NM_001256182.2:c.6797C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001256183.2:c.6797C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_013275.6:c.6797C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001151079	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely benign (Jan 1, 2023)	germline	clinical testing	Citation Link,
SCV001552952	Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR) See additional submitters Franklin by Genoox	no assertion criteria provided	Likely benign	unknown	clinical testing
SCV001766862	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (Jul 25, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001151079

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Likely benign
(Jan 1, 2023)

germline

clinical testing

Citation Link,

SCV001552952

Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided

Likely benign

unknown

clinical testing

SCV001766862

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely benign
(Jul 25, 2020)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	5	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV001151079.21

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

Description

ANKRD11: BP4, BS2

#	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		5	not provided	not provided	not provided

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001552952.1

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

Description

The ANKRD11 p.Ala2266Val variant was not identified in the literature but was identified in dbSNP (ID: rs748996527) and ClinVar (classified as likely benign by Genetic Services Laboratory, University of Chicago and CeGaT Praxis fuer Humangenetik Tuebingen). The variant was identified in control databases in 50 of 158488 chromosomes at a frequency of 0.0003155 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (non-Finnish) in 46 of 63862 chromosomes (freq: 0.00072), Other in 2 of 4934 chromosomes (freq: 0.000405), Ashkenazi Jewish in 1 of 7042 chromosomes (freq: 0.000142) and Latino in 1 of 24720 chromosomes (freq: 0.00004), but was not observed in the African, East Asian, European (Finnish), or South Asian populations. This frequency is greater than expected for autosomal dominant KBG syndrome (Swols_2017_PMID:29258554). The p.Ala2266 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

#	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 GeneDx, SCV001766862.1

#	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: Apr 15, 2024

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