16-89279962-G-C

Position:

chr16-89279962-G-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_013275.6(ANKRD11):c.6580C>G(p.Gln2194Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000243 in 1,610,456 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

ANKRD11
NM_013275.6 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 1.73

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:

ANKRD11 (HGNC:):

ANKRD11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.039126575).

BP6

Variant 16-89279962-G-C is Benign according to our data. Variant chr16-89279962-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 585419.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=4, Uncertain_significance=1}.

BS2

High AC in GnomAd4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD11	NM_013275.6 linkuse as main transcript	c.6580C>G	p.Gln2194Glu	missense_variant	9/13	ENST00000301030.10	NP_037407.4	Q6UB99
ANKRD11	NM_001256182.2 linkuse as main transcript	c.6580C>G	p.Gln2194Glu	missense_variant	10/14		NP_001243111.1	Q6UB99
ANKRD11	NM_001256183.2 linkuse as main transcript	c.6580C>G	p.Gln2194Glu	missense_variant	9/13		NP_001243112.1	Q6UB99

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD11	ENST00000301030.10 linkuse as main transcript	c.6580C>G	p.Gln2194Glu	missense_variant	9/13	5	NM_013275.6	ENSP00000301030.4		Q6UB99

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000234

AC:

AN:

239104

Hom.:

AF XY:

0.000183

AC XY:

AN XY:

131442

show subpopulations

Gnomad AFR exome

AF:

0.0000705

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000200

Gnomad NFE exome

AF:

0.000422

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.000252

AC:

367

AN:

1458262

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

176

AN XY:

725568

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000120

Gnomad4 NFE exome

AF:

0.000307

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000158

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000306

Hom.:

Bravo

AF:

0.000193

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000244

AC:

ExAC

AF:

0.000208

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000474

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	ANKRD11: BP4 -
Uncertain significance, criteria provided, single submitter	clinical testing	Athena Diagnostics	Dec 06, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

KBG syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 11, 2023

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 12, 2017

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

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 26, 2024

This variant is classified as likely 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

-0.48

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.4

DANN

Benign

0.19

DEOGEN2

Benign

0.083

T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.56

.;.;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.039

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;L;L

PrimateAI

Benign

0.31

PROVEAN

Benign

0.13

N;N;.

REVEL

Benign

0.033

Sift

Benign

0.50

T;T;.

Sift4G

Benign

1.0

T;T;.

Polyphen

0.0060

B;B;B

Vest4

0.081

MVP

0.26

MPC

0.093

ClinPred

0.016

GERP RS

2.3

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Varity_R

0.052

gMVP

0.017

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