rs372632879

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_013275.6(ANKRD11):c.6725C>T(p.Ala2242Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000337 in 1,543,466 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2242T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 2 hom. )

Consequence

ANKRD11
NM_013275.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.492

Publications

0 publications found

Variant links:

Genes affected

ANKRD11 (HGNC:21316): (ankyrin repeat domain containing 11) This locus encodes an ankryin repeat domain-containing protein. The encoded protein inhibits ligand-dependent activation of transcription. Mutations in this gene have been associated with KBG syndrome, which is characterized by macrodontia, distinctive craniofacial features, short stature, skeletal anomalies, global developmental delay, seizures and intellectual disability. Alternatively spliced transcript variants have been described. Related pseudogenes exist on chromosomes 2 and X. [provided by RefSeq, Jan 2012]

ANKRD11 Gene-Disease associations (from GenCC):

KBG syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, Illumina, ClinGen
congenital heart defects, multiple types
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ANKRD11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004374236).

BP6

Variant 16-89279817-G-A is Benign according to our data. Variant chr16-89279817-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 585423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89279817-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 585423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89279817-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 585423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89279817-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 585423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89279817-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 585423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89279817-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 585423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89279817-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 585423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89279817-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 585423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00142 (217/152310) while in subpopulation AFR AF = 0.00464 (193/41564). AF 95% confidence interval is 0.00411. There are 1 homozygotes in GnomAd4. There are 102 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 217 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD11	NM_013275.6 link	c.6725C>T	p.Ala2242Val	missense_variant	Exon 9 of 13	ENST00000301030.10	NP_037407.4	Q6UB99
ANKRD11	NM_001256182.2 link	c.6725C>T	p.Ala2242Val	missense_variant	Exon 10 of 14		NP_001243111.1	Q6UB99
ANKRD11	NM_001256183.2 link	c.6725C>T	p.Ala2242Val	missense_variant	Exon 9 of 13		NP_001243112.1	Q6UB99

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD11	ENST00000301030.10 link	c.6725C>T	p.Ala2242Val	missense_variant	Exon 9 of 13	5	NM_013275.6	ENSP00000301030.4		Q6UB99

Frequencies

GnomAD3 genomes

AF:

0.00142

AC:

216

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00463

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000981

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.000360

AC:

AN:

138858

AF XY:

0.000370

show subpopulations

Gnomad AFR exome

AF:

0.00523

Gnomad AMR exome

AF:

0.000489

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000587

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000218

AC:

303

AN:

1391156

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

159

AN XY:

686756

show subpopulations

African (AFR)

AF:

0.00509

AC:

161

AN:

31620

American (AMR)

AF:

0.000503

AC:

AN:

35812

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25160

East Asian (EAS)

AF:

0.00

AC:

AN:

35816

South Asian (SAS)

AF:

0.0000251

AC:

AN:

79564

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41200

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4698

European-Non Finnish (NFE)

AF:

0.0000963

AC:

104

AN:

1079404

Other (OTH)

AF:

0.000311

AC:

AN:

57882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00142

AC:

217

AN:

152310

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

102

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00464

AC:

193

AN:

41564

American (AMR)

AF:

0.000980

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68026

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000897

Hom.:

Bravo

AF:

0.00171

ESP6500AA

AF:

0.00257

AC:

ESP6500EA

AF:

0.000258

AC:

ExAC

AF:

0.000257

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ANKRD11: BP4, BS1 -

Feb 23, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 11, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

KBG syndrome

Benign:2

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Jul 26, 2021

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

ANKRD11-related disorder

Benign:1

Jan 13, 2020

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.76

(source)

DANN

Benign

0.24

DEOGEN2

Benign

0.068

T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.23

.;.;T

M_CAP

Benign

0.050

MetaRNN

Benign

0.0044

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.26

N;N;N

PhyloP100

-0.49

PrimateAI

Benign

0.33

PROVEAN

Benign

0.12

N;N;.

REVEL

Benign

0.0090

Sift

Benign

0.35

T;T;.

Sift4G

Benign

0.29

T;T;.

Polyphen

0.0010

B;B;B

Vest4

0.060

MVP

0.17

MPC

0.085

ClinPred

0.0054

GERP RS

0.045

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.013

gMVP

0.014

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over