Genetic Variant NM_001242809.2:c.1648G>A (chr6-89630468-G-A) – 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.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. 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 0.0061 ( 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

Publications

7 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:

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=0.0019686222).

BP6

Variant 6-89630468-G-A is Benign according to our data. Variant chr6-89630468-G-A is described in ClinVar as Benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
ANKRD6	NM_001242809.2 link	c.1648G>A	p.Ala550Thr	missense_variant	Exon 16 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.1648G>A	p.Ala550Thr	missense_variant	Exon 16 of 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

GnomAD2 exomes

AF:

0.0103

AC:

2551

AN:

248558

AF XY:

0.00986

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 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

African (AFR)

AF:

0.000269

AC:

AN:

33464

American (AMR)

AF:

0.000134

AC:

AN:

44662

Ashkenazi Jewish (ASJ)

AF:

0.000268

AC:

AN:

26084

East Asian (EAS)

AF:

0.0971

AC:

3855

AN:

39700

South Asian (SAS)

AF:

0.00282

AC:

243

AN:

86246

European-Finnish (FIN)

AF:

0.0262

AC:

1397

AN:

53382

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000592

AC:

658

AN:

1111682

Other (OTH)

AF:

0.00744

AC:

449

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

382

764

1147

1529

1911

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<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:

0.00606

AC:

923

AN:

152334

Hom.:

Cov.:

AF XY:

0.00799

AC XY:

595

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41582

American (AMR)

AF:

0.000588

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.0920

AC:

477

AN:

5184

South Asian (SAS)

AF:

0.00476

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0323

AC:

343

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000882

AC:

AN:

68030

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

143

190

238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00358

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

Feb 26, 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

0.074

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

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;.

PhyloP100

0.91

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

Mutation Taster

=94/6

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

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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