rs534182728

Positions:

chr16-89280417-T-C

Variant summary

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

The NM_013275.6(ANKRD11):c.6125A>G(p.Asp2042Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000453 in 1,565,852 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00045 ( 0 hom. )

Consequence

ANKRD11
NM_013275.6 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.78

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=0.017320007).

BP6

Variant 16-89280417-T-C is Benign according to our data. Variant chr16-89280417-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 589039.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000526 (80/152196) while in subpopulation AMR AF= 0.00248 (38/15302). AF 95% confidence interval is 0.00186. There are 0 homozygotes in gnomad4. There are 37 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 80 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD11	NM_013275.6 link	c.6125A>G	p.Asp2042Gly	missense_variant	9/13	ENST00000301030.10	NP_037407.4	Q6UB99
ANKRD11	NM_001256182.2 link	c.6125A>G	p.Asp2042Gly	missense_variant	10/14		NP_001243111.1	Q6UB99
ANKRD11	NM_001256183.2 link	c.6125A>G	p.Asp2042Gly	missense_variant	9/13		NP_001243112.1	Q6UB99

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD11	ENST00000301030.10 link	c.6125A>G	p.Asp2042Gly	missense_variant	9/13	5	NM_013275.6	ENSP00000301030.4		Q6UB99

Frequencies

GnomAD3 genomes

AF:

0.000526

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

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:

0.000500

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000256

AC:

AN:

191452

Hom.:

AF XY:

0.000245

AC XY:

AN XY:

106046

show subpopulations

Gnomad AFR exome

AF:

0.0000854

Gnomad AMR exome

AF:

0.000210

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000449

Gnomad OTH exome

AF:

0.000876

GnomAD4 exome

AF:

0.000446

AC:

630

AN:

1413656

Hom.:

Cov.:

AF XY:

0.000424

AC XY:

296

AN XY:

698094

show subpopulations

Gnomad4 AFR exome

AF:

0.0000311

Gnomad4 AMR exome

AF:

0.000578

Gnomad4 ASJ exome

AF:

0.0000426

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000622

Gnomad4 NFE exome

AF:

0.000534

Gnomad4 OTH exome

AF:

0.000363

GnomAD4 genome

AF:

0.000526

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000396

Hom.:

Bravo

AF:

0.00108

ExAC

AF:

0.000137

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	ANKRD11: BP4, BS1 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 28, 2021	This variant is associated with the following publications: (PMID: 25852444) -

KBG syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 11, 2023

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.70

CADD

Benign

9.9

DANN

Benign

0.75

DEOGEN2

Benign

0.082

T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.42

.;.;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.64

N;N;.

REVEL

Benign

0.028

Sift

Benign

0.32

T;T;.

Sift4G

Benign

0.11

T;T;.

Polyphen

0.0

B;B;B

Vest4

0.036

MVP

0.16

MPC

0.11

ClinPred

0.0092

GERP RS

0.0095

Varity_R

0.050

gMVP

0.064

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