rs2279348

Positions:

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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:6

Conservation

PhyloP100: 0.597

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 587797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89283630-G-A is described in Lovd as [Benign].

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/exons	MANE
ANKRD11	NM_013275.6 linkuse as main transcript	c.2912C>T	p.Ala971Val	missense_variant	9/13	ENST00000301030.10
ANKRD11	NM_001256182.2 linkuse as main transcript	c.2912C>T	p.Ala971Val	missense_variant	10/14
ANKRD11	NM_001256183.2 linkuse as main transcript	c.2912C>T	p.Ala971Val	missense_variant	9/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD11	ENST00000301030.10 linkuse as main transcript	c.2912C>T	p.Ala971Val	missense_variant	9/13	5	NM_013275.6	P1

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

GnomAD3 exomes

AF:

0.635

AC:

158132

AN:

248878

Hom.:

53105

AF XY:

0.640

AC XY:

86259

AN XY:

134742

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 SAS exome

AF:

0.613

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

Gnomad4 AFR exome

AF:

0.635

Gnomad4 AMR exome

AF:

0.584

Gnomad4 ASJ exome

AF:

0.838

Gnomad4 EAS exome

AF:

0.239

Gnomad4 SAS exome

AF:

0.611

Gnomad4 FIN exome

AF:

0.592

Gnomad4 NFE exome

AF:

0.734

Gnomad4 OTH exome

AF:

0.678

GnomAD4 genome

AF:

0.660

AC:

100413

AN:

152102

Hom.:

33999

Cov.:

AF XY:

0.647

AC XY:

48114

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.637

Gnomad4 AMR

AF:

0.620

Gnomad4 ASJ

AF:

0.849

Gnomad4 EAS

AF:

0.195

Gnomad4 SAS

AF:

0.597

Gnomad4 FIN

AF:

0.578

Gnomad4 NFE

AF:

0.724

Gnomad4 OTH

AF:

0.664

Alfa

AF:

0.710

Hom.:

56142

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:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

KBG syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 11, 2016

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

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

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;.

MutationTaster

Benign

1.0

P;P

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over