Variant rs2273238 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ANKRD6	NM_001242809.2 linkuse as main transcript	c.698C>T	p.Thr233Met	missense_variant	8/16	ENST00000339746.9
LOC124901359	XR_007059673.1 linkuse as main transcript	n.205+5080G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD6	ENST00000339746.9 linkuse as main transcript	c.698C>T	p.Thr233Met	missense_variant	8/16	1	NM_001242809.2	A1	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

GnomAD3 exomes

AF:

0.115

AC:

28717

AN:

249234

Hom.:

2772

AF XY:

0.110

AC XY:

14913

AN XY:

135208

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 SAS exome

AF:

0.184

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

Gnomad4 AFR exome

AF:

0.302

Gnomad4 AMR exome

AF:

0.194

Gnomad4 ASJ exome

AF:

0.0883

Gnomad4 EAS exome

AF:

0.251

Gnomad4 SAS exome

AF:

0.184

Gnomad4 FIN exome

AF:

0.0595

Gnomad4 NFE exome

AF:

0.0363

Gnomad4 OTH exome

AF:

0.0878

GnomAD4 genome

AF:

0.137

AC:

20876

AN:

152254

Hom.:

2408

Cov.:

AF XY:

0.140

AC XY:

10418

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.293

Gnomad4 AMR

AF:

0.160

Gnomad4 ASJ

AF:

0.0952

Gnomad4 EAS

AF:

0.258

Gnomad4 SAS

AF:

0.195

Gnomad4 FIN

AF:

0.0595

Gnomad4 NFE

AF:

0.0399

Gnomad4 OTH

AF:

0.122

Alfa

AF:

0.0654

Hom.:

1640

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

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

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;.;.

MutationTaster

Benign

1.0

P;P;P;P;P;P

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

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

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