Genetic Variant ANKRD6:p.Ile128Val (chr6-89606070-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001242809.2(ANKRD6):c.382A>G(p.Ile128Val) variant causes a missense change. The variant allele was found at a frequency of 0.834 in 1,587,258 control chromosomes in the GnomAD database, including 555,010 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.80 ( 49742 hom., cov: 33)

Exomes 𝑓: 0.84 ( 505268 hom. )

Consequence

ANKRD6
NM_001242809.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.00

Publications

34 publications found

Variant links:

Genes affected

ANKRD6 (HGNC:17280): (ankyrin repeat domain 6) Predicted to be involved in negative regulation of canonical Wnt signaling pathway and positive regulation of JNK cascade. Predicted to act upstream of or within positive regulation of Wnt signaling pathway, planar cell polarity pathway. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD6 links:

LYRM2 (HGNC:25229): (LYR motif containing 2)

LYRM2 links:

LOC124901359 (HGNC:):

LOC124901359 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.911872E-7).

BP6

Variant 6-89606070-A-G is Benign according to our data. Variant chr6-89606070-A-G is described in ClinVar as Benign. ClinVar VariationId is 3060685.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD6	NM_001242809.2 link	c.382A>G	p.Ile128Val	missense_variant	Exon 5 of 16	ENST00000339746.9	NP_001229738.1	Q9Y2G4-2B7Z3D2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD6	ENST00000339746.9 link	c.382A>G	p.Ile128Val	missense_variant	Exon 5 of 16	1	NM_001242809.2	ENSP00000345767.4		Q9Y2G4-2

Frequencies

GnomAD3 genomes

AF:

0.804

AC:

122356

AN:

152096

Hom.:

49724

Cov.:

show subpopulations

Gnomad AFR

AF:

0.691

Gnomad AMI

AF:

0.888

Gnomad AMR

AF:

0.866

Gnomad ASJ

AF:

0.832

Gnomad EAS

AF:

0.908

Gnomad SAS

AF:

0.698

Gnomad FIN

AF:

0.876

Gnomad MID

AF:

0.810

Gnomad NFE

AF:

0.845

Gnomad OTH

AF:

0.805

GnomAD2 exomes

AF:

0.830

AC:

178315

AN:

214964

AF XY:

0.823

show subpopulations

Gnomad AFR exome

AF:

0.693

Gnomad AMR exome

AF:

0.892

Gnomad ASJ exome

AF:

0.829

Gnomad EAS exome

AF:

0.905

Gnomad FIN exome

AF:

0.867

Gnomad NFE exome

AF:

0.846

Gnomad OTH exome

AF:

0.836

GnomAD4 exome

AF:

0.837

AC:

1201762

AN:

1435044

Hom.:

505268

Cov.:

AF XY:

0.833

AC XY:

592574

AN XY:

711126

show subpopulations

African (AFR)

AF:

0.688

AC:

22680

AN:

32982

American (AMR)

AF:

0.887

AC:

36731

AN:

41426

Ashkenazi Jewish (ASJ)

AF:

0.827

AC:

21114

AN:

25538

East Asian (EAS)

AF:

0.930

AC:

35994

AN:

38712

South Asian (SAS)

AF:

0.693

AC:

56432

AN:

81380

European-Finnish (FIN)

AF:

0.867

AC:

44954

AN:

51874

Middle Eastern (MID)

AF:

0.813

AC:

4628

AN:

5694

European-Non Finnish (NFE)

AF:

0.847

AC:

930210

AN:

1098074

Other (OTH)

AF:

0.826

AC:

49019

AN:

59364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

9110

18219

27329

36438

45548

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20974

41948

62922

83896

104870

<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:

0.804

AC:

122421

AN:

152214

Hom.:

49742

Cov.:

AF XY:

0.806

AC XY:

59960

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.691

AC:

28666

AN:

41512

American (AMR)

AF:

0.866

AC:

13241

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.832

AC:

2890

AN:

3472

East Asian (EAS)

AF:

0.909

AC:

4708

AN:

5180

South Asian (SAS)

AF:

0.700

AC:

3376

AN:

4824

European-Finnish (FIN)

AF:

0.876

AC:

9298

AN:

10610

Middle Eastern (MID)

AF:

0.813

AC:

239

AN:

294

European-Non Finnish (NFE)

AF:

0.845

AC:

57499

AN:

68012

Other (OTH)

AF:

0.804

AC:

1694

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1248

2497

3745

4994

6242

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

874

1748

2622

3496

4370

<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:

0.830

Hom.:

182175

Bravo

AF:

0.801

TwinsUK

AF:

0.842

AC:

3122

ALSPAC

AF:

0.852

AC:

3285

ESP6500AA

AF:

0.717

AC:

2952

ESP6500EA

AF:

0.843

AC:

7075

ExAC

AF:

0.808

AC:

96698

Asia WGS

AF:

0.749

AC:

2602

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ANKRD6-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as 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

0.065

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

6.9

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0041

.;T;.;T;T;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.28

T;.;T;T;T;T

MetaRNN

Benign

5.9e-7

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;L;L;.;L;.

PhyloP100

4.0

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.44

N;N;N;N;N;N

REVEL

Benign

0.093

Sift

Benign

1.0

T;T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T

Polyphen

0.0

B;B;.;.;B;.

Vest4

0.098

MPC

0.045

ClinPred

0.0028

GERP RS

4.1

Varity_R

0.021

gMVP

0.16

Mutation Taster

=90/10

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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