Variant rs9362667 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.1648G>A(p.Ala550Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00468 in 1,613,662 control chromosomes in the GnomAD database, including 245 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0061 ( 24 hom., cov: 33)

Exomes 𝑓: 0.0045 ( 221 hom. )

Consequence

ANKRD6
NM_001242809.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.907

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:

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=0.0019686222).

BP6

Variant 6-89630468-G-A is Benign according to our data. Variant chr6-89630468-G-A is described in ClinVar as [Benign]. Clinvar id is 3058841.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD6	NM_001242809.2 link	c.1648G>A	p.Ala550Thr	missense_variant	16/16	ENST00000339746.9	NP_001229738.1	Q9Y2G4-2B7Z3D2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD6	ENST00000339746.9 link	c.1648G>A	p.Ala550Thr	missense_variant	16/16	1	NM_001242809.2	ENSP00000345767.4		Q9Y2G4-2

Frequencies

GnomAD3 genomes

AF:

0.00609

AC:

927

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0924

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.0323

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000882

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.0103

AC:

2551

AN:

248558

Hom.:

AF XY:

0.00986

AC XY:

1330

AN XY:

134874

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.0000871

Gnomad ASJ exome

AF:

0.000200

Gnomad EAS exome

AF:

0.0934

Gnomad SAS exome

AF:

0.00239

Gnomad FIN exome

AF:

0.0281

Gnomad NFE exome

AF:

0.00132

Gnomad OTH exome

AF:

0.00597

GnomAD4 exome

AF:

0.00453

AC:

6627

AN:

1461328

Hom.:

221

Cov.:

AF XY:

0.00460

AC XY:

3343

AN XY:

726954

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.0971

Gnomad4 SAS exome

AF:

0.00282

Gnomad4 FIN exome

AF:

0.0262

Gnomad4 NFE exome

AF:

0.000592

Gnomad4 OTH exome

AF:

0.00744

GnomAD4 genome

AF:

0.00606

AC:

923

AN:

152334

Hom.:

Cov.:

AF XY:

0.00799

AC XY:

595

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0920

Gnomad4 SAS

AF:

0.00476

Gnomad4 FIN

AF:

0.0323

Gnomad4 NFE

AF:

0.000882

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00368

Hom.:

Bravo

AF:

0.00484

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000250

AC:

ESP6500EA

AF:

0.000598

AC:

ExAC

AF:

0.0101

AC:

1228

Asia WGS

AF:

0.0330

AC:

117

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000296

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 26, 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

0.074

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.49

DEOGEN2

Benign

0.013

.;T;.;T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.80

T;.;T;T;T

MetaRNN

Benign

0.0020

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

.;N;.;N;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.74

N;N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.20

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

B;B;.;B;.

Vest4

0.057

MPC

0.050

ClinPred

0.0034

GERP RS

4.2

Varity_R

0.052

gMVP

0.14

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