rs76793093

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_StrongBA1

The NM_013275.6(ANKRD11):c.6787C>T(p.Pro2263Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 1,523,960 control chromosomes in the GnomAD database, including 1,391 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 150 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1241 hom. )

Consequence

ANKRD11
NM_013275.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.306

Publications

12 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=0.0014477372).

BP6

Variant 16-89279755-G-A is Benign according to our data. Variant chr16-89279755-G-A is described in ClinVar as Benign. ClinVar VariationId is 380369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD11	NM_013275.6 link	c.6787C>T	p.Pro2263Ser	missense_variant	Exon 9 of 13	ENST00000301030.10	NP_037407.4	Q6UB99
ANKRD11	NM_001256182.2 link	c.6787C>T	p.Pro2263Ser	missense_variant	Exon 10 of 14		NP_001243111.1	Q6UB99
ANKRD11	NM_001256183.2 link	c.6787C>T	p.Pro2263Ser	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.6787C>T	p.Pro2263Ser	missense_variant	Exon 9 of 13	5	NM_013275.6	ENSP00000301030.4		Q6UB99

Frequencies

GnomAD3 genomes

AF:

0.0337

AC:

5121

AN:

152136

Hom.:

150

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00729

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0243

Gnomad ASJ

AF:

0.00952

Gnomad EAS

AF:

0.0627

Gnomad SAS

AF:

0.0155

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0381

Gnomad OTH

AF:

0.0254

GnomAD2 exomes

AF:

0.0331

AC:

4156

AN:

125568

AF XY:

0.0313

show subpopulations

Gnomad AFR exome

AF:

0.00541

Gnomad AMR exome

AF:

0.0301

Gnomad ASJ exome

AF:

0.00947

Gnomad EAS exome

AF:

0.0649

Gnomad FIN exome

AF:

0.122

Gnomad NFE exome

AF:

0.0353

Gnomad OTH exome

AF:

0.0347

GnomAD4 exome

AF:

0.0387

AC:

53029

AN:

1371706

Hom.:

1241

Cov.:

AF XY:

0.0376

AC XY:

25397

AN XY:

675234

show subpopulations

African (AFR)

AF:

0.00597

AC:

187

AN:

31338

American (AMR)

AF:

0.0302

AC:

1059

AN:

35106

Ashkenazi Jewish (ASJ)

AF:

0.0108

AC:

260

AN:

24154

East Asian (EAS)

AF:

0.0648

AC:

2311

AN:

35682

South Asian (SAS)

AF:

0.0115

AC:

907

AN:

78624

European-Finnish (FIN)

AF:

0.118

AC:

4027

AN:

34098

Middle Eastern (MID)

AF:

0.00809

AC:

AN:

4820

European-Non Finnish (NFE)

AF:

0.0395

AC:

42300

AN:

1070814

Other (OTH)

AF:

0.0340

AC:

1939

AN:

57070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

3743

7486

11230

14973

18716

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1648

3296

4944

6592

8240

<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:

0.0336

AC:

5122

AN:

152254

Hom.:

150

Cov.:

AF XY:

0.0375

AC XY:

2788

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.00727

AC:

302

AN:

41556

American (AMR)

AF:

0.0242

AC:

370

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00952

AC:

AN:

3468

East Asian (EAS)

AF:

0.0630

AC:

325

AN:

5156

South Asian (SAS)

AF:

0.0157

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.129

AC:

1371

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0381

AC:

2590

AN:

68002

Other (OTH)

AF:

0.0251

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

246

491

737

982

1228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0217

Hom.:

Bravo

AF:

0.0253

TwinsUK

AF:

0.0332

AC:

123

ALSPAC

AF:

0.0348

AC:

134

ESP6500AA

AF:

0.00467

AC:

ESP6500EA

AF:

0.0189

AC:

121

ExAC

AF:

0.0179

AC:

1784

Asia WGS

AF:

0.0420

AC:

147

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Feb 16, 2024

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 22, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

KBG syndrome

Benign:2

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Apr 18, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.2

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.067

T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.34

.;.;T

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.58

N;N;N

PhyloP100

-0.31

PrimateAI

Benign

0.45

PROVEAN

Benign

0.040

N;N;.

REVEL

Benign

0.030

Sift

Benign

0.26

T;T;.

Sift4G

Benign

0.81

T;T;.

Polyphen

0.0020

B;B;B

Vest4

0.019

MPC

0.087

ClinPred

0.0046

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.021

gMVP

0.022

Mutation Taster

=99/1

polymorphism (auto)

(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

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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