Variant 12-132727250-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_015114.3(ANKLE2):c.2809G>A(p.Ala937Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000289 in 1,556,838 control chromosomes in the GnomAD database, including 1 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

ANKLE2
NM_015114.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.260

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0043174922).

BP6

Variant 12-132727250-C-T is Benign according to our data. Variant chr12-132727250-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 755265.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKLE2	NM_015114.3 link	c.2809G>A	p.Ala937Thr	missense_variant	Exon 13 of 13	ENST00000357997.10	NP_055929.1	Q86XL3-1
ANKLE2	XM_005266159.4 link	c.2623G>A	p.Ala875Thr	missense_variant	Exon 13 of 13		XP_005266216.1
ANKLE2	XM_024448899.2 link	c.1498G>A	p.Ala500Thr	missense_variant	Exon 9 of 9		XP_024304667.1
ANKLE2	XM_006719735.2 link	c.*174G>A		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.2809G>A	p.Ala937Thr	missense_variant	Exon 13 of 13	1	NM_015114.3	ENSP00000350686.5		Q86XL3-1

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

214

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00480

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000297

AC:

AN:

165254

Hom.:

AF XY:

0.000270

AC XY:

AN XY:

88978

show subpopulations

Gnomad AFR exome

AF:

0.00460

Gnomad AMR exome

AF:

0.000152

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000904

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000167

AC:

235

AN:

1404454

Hom.:

Cov.:

AF XY:

0.000153

AC XY:

106

AN XY:

692972

show subpopulations

Gnomad4 AFR exome

AF:

0.00407

Gnomad4 AMR exome

AF:

0.000214

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.0000207

Gnomad4 NFE exome

AF:

0.0000721

Gnomad4 OTH exome

AF:

0.000258

GnomAD4 genome

AF:

0.00141

AC:

215

AN:

152384

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.00481

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000139

Hom.:

Bravo

AF:

0.00161

ESP6500AA

AF:

0.00241

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000423

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ANKLE2-related disorder

Benign:1

Aug 30, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Jul 05, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.68

CADD

Benign

9.4

DANN

Benign

0.97

DEOGEN2

Benign

0.0053

T;.;.

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.52

T;.;T

MetaRNN

Benign

0.0043

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;.;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.021

Sift

Benign

0.14

T;T;T

Sift4G

Benign

0.25

T;T;T

Polyphen

0.23

B;.;.

Vest4

0.023

MVP

0.17

MPC

0.090

ClinPred

0.026

GERP RS

0.59

Varity_R

0.041

gMVP

0.51

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