Variant chr2-189676771-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378068.1(ANKAR):c.281T>G(p.Leu94Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 1,614,174 control chromosomes in the GnomAD database, including 132 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L94P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.016 ( 67 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 65 hom. )

Consequence

ANKAR
NM_001378068.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.14

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00252074).

BP6

Variant 2-189676771-T-G is Benign according to our data. Variant chr2-189676771-T-G is described in ClinVar as [Benign]. Clinvar id is 791881.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKAR	NM_001378068.1 linkuse as main transcript	c.281T>G	p.Leu94Arg	missense_variant	2/23	ENST00000684021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKAR	ENST00000684021.1 linkuse as main transcript	c.281T>G	p.Leu94Arg	missense_variant	2/23		NM_001378068.1	P1	Q7Z5J8-1

Frequencies

GnomAD3 genomes

AF:

0.0162

AC:

2471

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0560

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00661

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.00410

AC:

1029

AN:

251000

Hom.:

AF XY:

0.00315

AC XY:

427

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.0564

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00176

AC:

2576

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

1131

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0606

Gnomad4 AMR exome

AF:

0.00288

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000103

Gnomad4 OTH exome

AF:

0.00440

GnomAD4 genome

AF:

0.0163

AC:

2480

AN:

152312

Hom.:

Cov.:

AF XY:

0.0160

AC XY:

1194

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0561

Gnomad4 AMR

AF:

0.00660

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.0000928

Hom.:

Bravo

AF:

0.0186

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0508

AC:

224

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00506

AC:

614

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.0041

T;T

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.58

.;T

MetaRNN

Benign

0.0025

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

0.58

N;N

REVEL

Benign

0.067

Sift

Benign

0.63

T;T

Sift4G

Benign

0.64

T;T

Polyphen

0.0030

B;B

Vest4

0.46

MVP

0.30

MPC

0.15

ClinPred

0.0028

GERP RS

1.6

Varity_R

0.11

gMVP

0.11

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