rs534329317

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBS1BS2

The NM_013275.6(ANKRD11):c.4475_4498delTCCTGCGGCATCACAGGGACGAGC(p.Leu1492_Glu1499del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000493 in 1,613,712 control chromosomes in the GnomAD database, including 2 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00043 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00050 ( 1 hom. )

Consequence

ANKRD11
NM_013275.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.291

Publications

0 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 -14 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_013275.6.

BP6

Variant 16-89282043-TGCTCGTCCCTGTGATGCCGCAGGA-T is Benign according to our data. Variant chr16-89282043-TGCTCGTCCCTGTGATGCCGCAGGA-T is described in ClinVar as Likely_benign. ClinVar VariationId is 772792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000434 (66/152238) while in subpopulation SAS AF = 0.00311 (15/4816). AF 95% confidence interval is 0.00192. There are 1 homozygotes in GnomAd4. There are 36 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 66 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD11	NM_013275.6 link	c.4475_4498delTCCTGCGGCATCACAGGGACGAGC	p.Leu1492_Glu1499del	disruptive_inframe_deletion	Exon 9 of 13	ENST00000301030.10	NP_037407.4	Q6UB99
ANKRD11	NM_001256182.2 link	c.4475_4498delTCCTGCGGCATCACAGGGACGAGC	p.Leu1492_Glu1499del	disruptive_inframe_deletion	Exon 10 of 14		NP_001243111.1	Q6UB99
ANKRD11	NM_001256183.2 link	c.4475_4498delTCCTGCGGCATCACAGGGACGAGC	p.Leu1492_Glu1499del	disruptive_inframe_deletion	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.4475_4498delTCCTGCGGCATCACAGGGACGAGC	p.Leu1492_Glu1499del	disruptive_inframe_deletion	Exon 9 of 13	5	NM_013275.6	ENSP00000301030.4		Q6UB99

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000697

AC:

175

AN:

250986

AF XY:

0.000869

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000607

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000499

AC:

730

AN:

1461474

Hom.:

AF XY:

0.000600

AC XY:

436

AN XY:

727042

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000119

AC:

AN:

33480

American (AMR)

AF:

0.000581

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00268

AC:

231

AN:

86258

European-Finnish (FIN)

AF:

0.0000377

AC:

AN:

53010

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000396

AC:

440

AN:

1112008

Other (OTH)

AF:

0.000364

AC:

AN:

60392

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.399

Heterozygous variant carriers

121

161

201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000434

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0000963

AC:

AN:

41546

American (AMR)

AF:

0.000719

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00311

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000500

AC:

AN:

68010

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000218

Hom.:

Bravo

AF:

0.000291

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000711

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

KBG syndrome

Benign:2

Jul 16, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

May 13, 2022

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not provided

Benign:1

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ANKRD11: PM4, BS1 -

ANKRD11-related disorder

Benign:1

Jun 27, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

PhyloP100

0.29

Mutation Taster

=147/53

polymorphism

(source)

Splicing

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