12-132727387-C-G

Variant names:

Variant summary

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

The NM_015114.3(ANKLE2):c.2672G>C(p.Gly891Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.07 in 1,560,976 control chromosomes in the GnomAD database, including 4,229 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 (★★).

Frequency

Genomes: 𝑓 0.058 ( 337 hom., cov: 33)

Exomes 𝑓: 0.071 ( 3892 hom. )

Consequence

ANKLE2
NM_015114.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.599

Variant links:

Genes affected

ANKLE2 (HGNC:29101): (ankyrin repeat and LEM domain containing 2) This gene encodes a member of the LEM family of inner nuclear membrane proteins. The encoded protein functions as a mitotic regulator through postmitotic formation of the nuclear envelope. Mutations in this gene cause morphology defects in the nuclear envelope and BAF hyperphosphorylation. [provided by RefSeq, Mar 2014]

ANKLE2 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=0.0018227398).

BP6

Variant 12-132727387-C-G is Benign according to our data. Variant chr12-132727387-C-G is described in ClinVar as [Benign]. Clinvar id is 1098724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKLE2	NM_015114.3 link	c.2672G>C	p.Gly891Ala	missense_variant	Exon 13 of 13	ENST00000357997.10	NP_055929.1	Q86XL3-1
ANKLE2	XM_005266159.4 link	c.2486G>C	p.Gly829Ala	missense_variant	Exon 13 of 13		XP_005266216.1
ANKLE2	XM_024448899.2 link	c.1361G>C	p.Gly454Ala	missense_variant	Exon 9 of 9		XP_024304667.1
ANKLE2	XM_006719735.2 link	c.*37G>C		3_prime_UTR_variant	Exon 12 of 12		XP_006719798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKLE2	ENST00000357997.10 link	c.2672G>C	p.Gly891Ala	missense_variant	Exon 13 of 13	1	NM_015114.3	ENSP00000350686.5		Q86XL3-1

Frequencies

GnomAD3 genomes

AF:

0.0577

AC:

8782

AN:

152228

Hom.:

337

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0122

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.0484

Gnomad ASJ

AF:

0.0971

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.0592

Gnomad FIN

AF:

0.0926

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0757

Gnomad OTH

AF:

0.0525

GnomAD3 exomes

AF:

0.0663

AC:

11057

AN:

166844

Hom.:

443

AF XY:

0.0672

AC XY:

5971

AN XY:

88810

show subpopulations

Gnomad AFR exome

AF:

0.0101

Gnomad AMR exome

AF:

0.0363

Gnomad ASJ exome

AF:

0.0948

Gnomad EAS exome

AF:

0.112

Gnomad SAS exome

AF:

0.0543

Gnomad FIN exome

AF:

0.0886

Gnomad NFE exome

AF:

0.0712

Gnomad OTH exome

AF:

0.0831

GnomAD4 exome

AF:

0.0713

AC:

100422

AN:

1408630

Hom.:

3892

Cov.:

AF XY:

0.0712

AC XY:

49557

AN XY:

695646

show subpopulations

Gnomad4 AFR exome

AF:

0.0102

Gnomad4 AMR exome

AF:

0.0364

Gnomad4 ASJ exome

AF:

0.0960

Gnomad4 EAS exome

AF:

0.112

Gnomad4 SAS exome

AF:

0.0525

Gnomad4 FIN exome

AF:

0.0875

Gnomad4 NFE exome

AF:

0.0730

Gnomad4 OTH exome

AF:

0.0722

GnomAD4 genome

AF:

0.0576

AC:

8778

AN:

152346

Hom.:

337

Cov.:

AF XY:

0.0584

AC XY:

4348

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0121

Gnomad4 AMR

AF:

0.0483

Gnomad4 ASJ

AF:

0.0971

Gnomad4 EAS

AF:

0.107

Gnomad4 SAS

AF:

0.0588

Gnomad4 FIN

AF:

0.0926

Gnomad4 NFE

AF:

0.0757

Gnomad4 OTH

AF:

0.0534

Alfa

AF:

0.0719

Hom.:

129

Bravo

AF:

0.0521

TwinsUK

AF:

0.0720

AC:

267

ALSPAC

AF:

0.0765

AC:

295

ESP6500AA

AF:

0.00945

AC:

ESP6500EA

AF:

0.0608

AC:

509

ExAC

AF:

0.0410

AC:

4705

Asia WGS

AF:

0.0980

AC:

341

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 31, 2018

GeneDx

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

- -

Microcephaly 16, primary, autosomal recessive

Benign:1

May 18, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.70

CADD

Benign

1.3

DANN

Benign

0.58

DEOGEN2

Benign

0.0036

T;.;.;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.68

T;.;T;T

MetaRNN

Benign

0.0018

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.;.;.

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.43

N;N;N;N

REVEL

Benign

0.063

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.17

B;.;.;.

Vest4

0.067

MPC

0.11

ClinPred

0.0032

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.019

gMVP

0.17

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