Variant chr12-132727252-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015114.3(ANKLE2):c.2807C>T(p.Ala936Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000057 in 1,404,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

ANKLE2
NM_015114.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.96

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15792125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKLE2	NM_015114.3 link	c.2807C>T	p.Ala936Val	missense_variant	Exon 13 of 13	ENST00000357997.10	NP_055929.1	Q86XL3-1
ANKLE2	XM_005266159.4 link	c.2621C>T	p.Ala874Val	missense_variant	Exon 13 of 13		XP_005266216.1
ANKLE2	XM_024448899.2 link	c.1496C>T	p.Ala499Val	missense_variant	Exon 9 of 9		XP_024304667.1
ANKLE2	XM_006719735.2 link	c.*172C>T		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.2807C>T	p.Ala936Val	missense_variant	Exon 13 of 13	1	NM_015114.3	ENSP00000350686.5		Q86XL3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000570

AC:

AN:

1404570

Hom.:

Cov.:

AF XY:

0.00000577

AC XY:

AN XY:

693012

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000274

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000370

Gnomad4 OTH exome

AF:

0.0000516

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Oct 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2807C>T (p.A936V) alteration is located in exon 13 (coding exon 13) of the ANKLE2 gene. This alteration results from a C to T substitution at nucleotide position 2807, causing the alanine (A) at amino acid position 936 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

T;.;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.65

T;.;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.8

L;.;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.025

D;D;D

Sift4G

Uncertain

0.056

T;T;T

Polyphen

0.19

B;.;.

Vest4

0.12

MutPred

0.32

Loss of disorder (P = 0.1297);.;.;

MVP

0.54

MPC

0.093

ClinPred

0.14

GERP RS

6.0

Varity_R

0.057

gMVP

0.53

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