rs2279348

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.2912C>T(p.Ala971Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 1,610,090 control chromosomes in the GnomAD database, including 399,541 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 0.66 ( 33999 hom., cov: 33)

Exomes 𝑓: 0.70 ( 365542 hom. )

Consequence

ANKRD11
NM_013275.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.597

Publications

37 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=1.1363677E-6).

BP6

Variant 16-89283630-G-A is Benign according to our data. Variant chr16-89283630-G-A is described in ClinVar as Benign. ClinVar VariationId is 587797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD11	NM_013275.6 link	c.2912C>T	p.Ala971Val	missense_variant	Exon 9 of 13	ENST00000301030.10	NP_037407.4	Q6UB99
ANKRD11	NM_001256182.2 link	c.2912C>T	p.Ala971Val	missense_variant	Exon 10 of 14		NP_001243111.1	Q6UB99
ANKRD11	NM_001256183.2 link	c.2912C>T	p.Ala971Val	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.2912C>T	p.Ala971Val	missense_variant	Exon 9 of 13	5	NM_013275.6	ENSP00000301030.4		Q6UB99

Frequencies

GnomAD3 genomes

AF:

0.660

AC:

100354

AN:

151984

Hom.:

33988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.637

Gnomad AMI

AF:

0.814

Gnomad AMR

AF:

0.620

Gnomad ASJ

AF:

0.849

Gnomad EAS

AF:

0.195

Gnomad SAS

AF:

0.596

Gnomad FIN

AF:

0.578

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.724

Gnomad OTH

AF:

0.671

GnomAD2 exomes

AF:

0.635

AC:

158132

AN:

248878

AF XY:

0.640

show subpopulations

Gnomad AFR exome

AF:

0.632

Gnomad AMR exome

AF:

0.582

Gnomad ASJ exome

AF:

0.830

Gnomad EAS exome

AF:

0.177

Gnomad FIN exome

AF:

0.583

Gnomad NFE exome

AF:

0.723

Gnomad OTH exome

AF:

0.664

GnomAD4 exome

AF:

0.701

AC:

1022165

AN:

1457988

Hom.:

365542

Cov.:

112

AF XY:

0.700

AC XY:

507825

AN XY:

725470

show subpopulations

African (AFR)

AF:

0.635

AC:

21268

AN:

33480

American (AMR)

AF:

0.584

AC:

26112

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.838

AC:

21914

AN:

26136

East Asian (EAS)

AF:

0.239

AC:

9502

AN:

39698

South Asian (SAS)

AF:

0.611

AC:

52661

AN:

86256

European-Finnish (FIN)

AF:

0.592

AC:

29326

AN:

49576

Middle Eastern (MID)

AF:

0.705

AC:

4064

AN:

5768

European-Non Finnish (NFE)

AF:

0.734

AC:

816387

AN:

1111984

Other (OTH)

AF:

0.678

AC:

40931

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

22427

44854

67281

89708

112135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19944

39888

59832

79776

99720

<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:

0.660

AC:

100413

AN:

152102

Hom.:

33999

Cov.:

AF XY:

0.647

AC XY:

48114

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.637

AC:

26400

AN:

41446

American (AMR)

AF:

0.620

AC:

9491

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.849

AC:

2947

AN:

3470

East Asian (EAS)

AF:

0.195

AC:

1008

AN:

5170

South Asian (SAS)

AF:

0.597

AC:

2877

AN:

4822

European-Finnish (FIN)

AF:

0.578

AC:

6118

AN:

10586

Middle Eastern (MID)

AF:

0.711

AC:

209

AN:

294

European-Non Finnish (NFE)

AF:

0.724

AC:

49218

AN:

67992

Other (OTH)

AF:

0.664

AC:

1403

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1649

3298

4948

6597

8246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

794

1588

2382

3176

3970

<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:

0.700

Hom.:

89561

Bravo

AF:

0.664

TwinsUK

AF:

0.743

AC:

2754

ALSPAC

AF:

0.743

AC:

2864

ESP6500AA

AF:

0.636

AC:

2794

ESP6500EA

AF:

0.728

AC:

6263

ExAC

AF:

0.637

AC:

77369

Asia WGS

AF:

0.416

AC:

1446

AN:

3478

EpiCase

AF:

0.734

EpiControl

AF:

0.731

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

KBG syndrome

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 14, 2021

Genome-Nilou Lab

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

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Mar 11, 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

0.084

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.37

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.085

T;T;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.33

.;.;T;T

MetaRNN

Benign

0.0000011

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.2

L;L;L;.

PhyloP100

0.60

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.020

N;N;.;.

REVEL

Benign

0.026

Sift

Benign

0.46

T;T;.;.

Sift4G

Benign

0.23

T;T;.;.

Polyphen

0.014

B;B;B;.

Vest4

0.0080

MPC

0.085

ClinPred

0.0051

GERP RS

-3.5

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

3.3

Varity_R

0.015

gMVP

0.00081

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