dbSNP rs2273238: ANKRD6:p.Thr233Met (chr6-89616641-C-T) – 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.698C>T(p.Thr233Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0726 in 1,613,750 control chromosomes in the GnomAD database, including 9,146 homozygotes. 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 Benign (no stars).

Frequency

Genomes: 𝑓 0.14 ( 2408 hom., cov: 33)

Exomes 𝑓: 0.066 ( 6738 hom. )

Consequence

ANKRD6
NM_001242809.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.41

Publications

19 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=0.0060423315).

BP6

Variant 6-89616641-C-T is Benign according to our data. Variant chr6-89616641-C-T is described in ClinVar as [Benign]. Clinvar id is 3060427.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD6	NM_001242809.2 link	c.698C>T	p.Thr233Met	missense_variant	Exon 8 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.698C>T	p.Thr233Met	missense_variant	Exon 8 of 16	1	NM_001242809.2	ENSP00000345767.4		Q9Y2G4-2

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20837

AN:

152136

Hom.:

2401

Cov.:

show subpopulations

Gnomad AFR

AF:

0.293

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.159

Gnomad ASJ

AF:

0.0952

Gnomad EAS

AF:

0.256

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.0595

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0399

Gnomad OTH

AF:

0.121

GnomAD2 exomes

AF:

0.115

AC:

28717

AN:

249234

AF XY:

0.110

show subpopulations

Gnomad AFR exome

AF:

0.296

Gnomad AMR exome

AF:

0.198

Gnomad ASJ exome

AF:

0.0885

Gnomad EAS exome

AF:

0.248

Gnomad FIN exome

AF:

0.0623

Gnomad NFE exome

AF:

0.0394

Gnomad OTH exome

AF:

0.0891

GnomAD4 exome

AF:

0.0658

AC:

96227

AN:

1461496

Hom.:

6738

Cov.:

AF XY:

0.0683

AC XY:

49631

AN XY:

727010

show subpopulations

African (AFR)

AF:

0.302

AC:

10090

AN:

33454

American (AMR)

AF:

0.194

AC:

8677

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0883

AC:

2308

AN:

26132

East Asian (EAS)

AF:

0.251

AC:

9953

AN:

39694

South Asian (SAS)

AF:

0.184

AC:

15862

AN:

86244

European-Finnish (FIN)

AF:

0.0595

AC:

3179

AN:

53398

Middle Eastern (MID)

AF:

0.0850

AC:

490

AN:

5768

European-Non Finnish (NFE)

AF:

0.0363

AC:

40366

AN:

1111728

Other (OTH)

AF:

0.0878

AC:

5302

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

4524

9047

13571

18094

22618

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1946

3892

5838

7784

9730

<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:

0.137

AC:

20876

AN:

152254

Hom.:

2408

Cov.:

AF XY:

0.140

AC XY:

10418

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.293

AC:

12162

AN:

41526

American (AMR)

AF:

0.160

AC:

2444

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0952

AC:

330

AN:

3468

East Asian (EAS)

AF:

0.258

AC:

1332

AN:

5170

South Asian (SAS)

AF:

0.195

AC:

940

AN:

4828

European-Finnish (FIN)

AF:

0.0595

AC:

631

AN:

10612

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0399

AC:

2715

AN:

68028

Other (OTH)

AF:

0.122

AC:

258

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

837

1675

2512

3350

4187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

224

448

672

896

1120

<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:

0.0737

Hom.:

3903

Bravo

AF:

0.148

TwinsUK

AF:

0.0343

AC:

127

ALSPAC

AF:

0.0319

AC:

123

ESP6500AA

AF:

0.264

AC:

1063

ESP6500EA

AF:

0.0389

AC:

326

ExAC

AF:

0.114

AC:

13780

Asia WGS

AF:

0.234

AC:

810

AN:

3478

EpiCase

AF:

0.0427

EpiControl

AF:

0.0394

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ANKRD6-related disorder

Benign:1

Oct 18, 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

0.12

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0057

.;T;.;T;T;.

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.76

T;.;T;T;T;T

MetaRNN

Benign

0.0060

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.46

N;N;N;N;.;.

PhyloP100

1.4

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.3

N;N;N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.11

T;T;T;T;T;T

Sift4G

Benign

0.14

T;T;T;T;T;T

Polyphen

0.72

P;P;.;P;.;.

Vest4

0.17

MPC

0.11

ClinPred

0.016

GERP RS

1.6

Varity_R

0.016

gMVP

0.25

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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