rs202081612

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_013275.6(ANKRD11):c.6745C>T(p.Arg2249Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 1,538,542 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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. R2249H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

ANKRD11
NM_013275.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.565

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034091175).

BP6

Variant 16-89279797-G-A is Benign according to our data. Variant chr16-89279797-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 445313.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89279797-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0011 (167/152296) while in subpopulation AFR AF= 0.00385 (160/41566). AF 95% confidence interval is 0.00336. There are 0 homozygotes in gnomad4. There are 71 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 167 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD11	NM_013275.6 link	c.6745C>T	p.Arg2249Cys	missense_variant	Exon 9 of 13	ENST00000301030.10	NP_037407.4	Q6UB99
ANKRD11	NM_001256182.2 link	c.6745C>T	p.Arg2249Cys	missense_variant	Exon 10 of 14		NP_001243111.1	Q6UB99
ANKRD11	NM_001256183.2 link	c.6745C>T	p.Arg2249Cys	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.6745C>T	p.Arg2249Cys	missense_variant	Exon 9 of 13	5	NM_013275.6	ENSP00000301030.4		Q6UB99

Frequencies

GnomAD3 genomes

AF:

0.00109

AC:

166

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00384

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000261

AC:

AN:

134218

Hom.:

AF XY:

0.000150

AC XY:

AN XY:

73426

show subpopulations

Gnomad AFR exome

AF:

0.00423

Gnomad AMR exome

AF:

0.000164

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000944

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000606

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000131

AC:

182

AN:

1386246

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

684146

show subpopulations

Gnomad4 AFR exome

AF:

0.00390

Gnomad4 AMR exome

AF:

0.000168

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000839

Gnomad4 SAS exome

AF:

0.0000503

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000260

Gnomad4 OTH exome

AF:

0.000225

GnomAD4 genome

AF:

0.00110

AC:

167

AN:

152296

Hom.:

Cov.:

AF XY:

0.000953

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00385

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000568

Hom.:

Bravo

AF:

0.00108

ESP6500AA

AF:

0.00280

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000198

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 24, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ANKRD11: BP4, BS1 -

Jan 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

KBG syndrome

Benign:3

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely 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

- -

Dec 22, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Jun 14, 2019

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

May 18, 2018

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

-0.63

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.077

T;T;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.73

.;.;T

MetaRNN

Benign

0.0034

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.76

N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

0.17

N;N;.

REVEL

Benign

0.028

Sift

Benign

0.051

T;T;.

Sift4G

Uncertain

0.051

T;T;.

Polyphen

0.0050

B;B;B

Vest4

0.082

MVP

0.22

MPC

0.12

ClinPred

0.021

GERP RS

-3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.043

gMVP

0.032

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