chr2-189689541-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001378068.1(ANKAR):c.616A>G(p.Thr206Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0011 in 1,577,898 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0062 ( 17 hom., cov: 32)

Exomes 𝑓: 0.00056 ( 11 hom. )

Consequence

ANKAR
NM_001378068.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.29

Publications

2 publications found

Variant links:

Genes affected

ANKAR (HGNC:26350): (ankyrin and armadillo repeat containing) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ANKAR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005278468).

BP6

Variant 2-189689541-A-G is Benign according to our data. Variant chr2-189689541-A-G is described in CliVar as Benign. Clinvar id is 716762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-189689541-A-G is described in CliVar as Benign. Clinvar id is 716762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-189689541-A-G is described in CliVar as Benign. Clinvar id is 716762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-189689541-A-G is described in CliVar as Benign. Clinvar id is 716762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-189689541-A-G is described in CliVar as Benign. Clinvar id is 716762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00616 (938/152322) while in subpopulation AFR AF = 0.021 (874/41562). AF 95% confidence interval is 0.0199. There are 17 homozygotes in GnomAd4. There are 450 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKAR	NM_001378068.1 link	c.616A>G	p.Thr206Ala	missense_variant	Exon 3 of 23	ENST00000684021.1	NP_001364997.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKAR	ENST00000684021.1 link	c.616A>G	p.Thr206Ala	missense_variant	Exon 3 of 23		NM_001378068.1	ENSP00000507233.1		Q7Z5J8-1

Frequencies

GnomAD3 genomes

AF:

0.00616

AC:

938

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0211

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00717

GnomAD2 exomes

AF:

0.00168

AC:

371

AN:

221296

AF XY:

0.00126

show subpopulations

Gnomad AFR exome

AF:

0.0217

Gnomad AMR exome

AF:

0.000883

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000763

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000564

AC:

804

AN:

1425576

Hom.:

Cov.:

AF XY:

0.000448

AC XY:

317

AN XY:

707256

show subpopulations

African (AFR)

AF:

0.0207

AC:

653

AN:

31544

American (AMR)

AF:

0.00106

AC:

AN:

35952

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24346

East Asian (EAS)

AF:

0.00

AC:

AN:

39120

South Asian (SAS)

AF:

0.000138

AC:

AN:

79908

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52358

Middle Eastern (MID)

AF:

0.000538

AC:

AN:

5572

European-Non Finnish (NFE)

AF:

0.0000146

AC:

AN:

1098026

Other (OTH)

AF:

0.00141

AC:

AN:

58750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

112

149

186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.00616

AC:

938

AN:

152322

Hom.:

Cov.:

AF XY:

0.00604

AC XY:

450

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0210

AC:

874

AN:

41562

American (AMR)

AF:

0.00268

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68026

Other (OTH)

AF:

0.00710

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

115

153

191

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:

0.00199

Hom.:

Bravo

AF:

0.00689

ESP6500AA

AF:

0.0220

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00202

AC:

245

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0052

T;T

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.67

.;T

MetaRNN

Benign

0.0053

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L

PhyloP100

4.3

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.35

N;N

REVEL

Benign

0.037

Sift

Benign

0.16

T;T

Sift4G

Uncertain

0.017

D;D

Polyphen

0.45

B;B

Vest4

0.20

MVP

0.70

MPC

0.22

ClinPred

0.028

GERP RS

4.8

Varity_R

0.071

gMVP

0.35

Mutation Taster

=99/1

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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