Variant 6-89606052-C-G 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.364C>G(p.Gln122Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0297 in 1,595,912 control chromosomes in the GnomAD database, including 1,446 homozygotes. In-silico tool predicts 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 0.037 ( 155 hom., cov: 33)

Exomes 𝑓: 0.029 ( 1291 hom. )

Consequence

ANKRD6
NM_001242809.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.57

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001758337).

BP6

Variant 6-89606052-C-G is Benign according to our data. Variant chr6-89606052-C-G is described in ClinVar as [Benign]. Clinvar id is 3041275.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.122 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.364C>G	p.Gln122Glu	missense_variant	5/16	ENST00000339746.9
LOC124901359	XR_007059673.1 linkuse as main transcript	n.206-121G>C		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.364C>G	p.Gln122Glu	missense_variant	5/16	1	NM_001242809.2	A1	Q9Y2G4-2

Frequencies

GnomAD3 genomes

AF:

0.0366

AC:

5567

AN:

152114

Hom.:

157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0588

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0240

Gnomad ASJ

AF:

0.0651

Gnomad EAS

AF:

0.0422

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.0229

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0199

Gnomad OTH

AF:

0.0363

GnomAD3 exomes

AF:

0.0417

AC:

9355

AN:

224118

Hom.:

387

AF XY:

0.0447

AC XY:

5380

AN XY:

120462

show subpopulations

Gnomad AFR exome

AF:

0.0572

Gnomad AMR exome

AF:

0.0305

Gnomad ASJ exome

AF:

0.0635

Gnomad EAS exome

AF:

0.0406

Gnomad SAS exome

AF:

0.134

Gnomad FIN exome

AF:

0.0263

Gnomad NFE exome

AF:

0.0205

Gnomad OTH exome

AF:

0.0366

GnomAD4 exome

AF:

0.0290

AC:

41813

AN:

1443680

Hom.:

1291

Cov.:

AF XY:

0.0315

AC XY:

22526

AN XY:

716074

show subpopulations

Gnomad4 AFR exome

AF:

0.0655

Gnomad4 AMR exome

AF:

0.0305

Gnomad4 ASJ exome

AF:

0.0619

Gnomad4 EAS exome

AF:

0.0310

Gnomad4 SAS exome

AF:

0.125

Gnomad4 FIN exome

AF:

0.0263

Gnomad4 NFE exome

AF:

0.0194

Gnomad4 OTH exome

AF:

0.0377

GnomAD4 genome

AF:

0.0367

AC:

5582

AN:

152232

Hom.:

155

Cov.:

AF XY:

0.0386

AC XY:

2875

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0589

Gnomad4 AMR

AF:

0.0239

Gnomad4 ASJ

AF:

0.0651

Gnomad4 EAS

AF:

0.0417

Gnomad4 SAS

AF:

0.130

Gnomad4 FIN

AF:

0.0229

Gnomad4 NFE

AF:

0.0199

Gnomad4 OTH

AF:

0.0397

Alfa

AF:

0.0227

Hom.:

Bravo

AF:

0.0364

TwinsUK

AF:

0.0165

AC:

ALSPAC

AF:

0.0163

AC:

ESP6500AA

AF:

0.0567

AC:

231

ESP6500EA

AF:

0.0211

AC:

177

ExAC

AF:

0.0405

AC:

4885

Asia WGS

AF:

0.109

AC:

380

AN:

3478

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

Feb 19, 2020

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

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0017

.;T;.;T;T;T

Eigen

Benign

-0.019

Eigen_PC

Benign

0.18

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;.;D;D;D;D

MetaRNN

Benign

0.0018

T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-1.2

N;N;N;.;N;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.86

N;N;N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.43

T;T;T;T;T;T

Sift4G

Benign

0.72

T;T;T;T;T;T

Polyphen

0.83

P;P;.;.;P;.

Vest4

0.49

MPC

0.23

ClinPred

0.035

GERP RS

5.0

Varity_R

0.14

gMVP

0.36

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