Variant 12-132727560-C-T 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_015114.3(ANKLE2):c.2616-117G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 50 hom., cov: 0)

Exomes 𝑓: 0.37 ( 50012 hom. )

Failed GnomAD Quality Control

Consequence

ANKLE2
NM_015114.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.27

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 (BayesDel_noAF=-0.95).

BP6

Variant 12-132727560-C-T is Benign according to our data. Variant chr12-132727560-C-T is described in ClinVar as [Benign]. Clinvar id is 1253390.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ANKLE2	NM_015114.3 link	c.2616-117G>A	intron_variant	Intron 12 of 12	ENST00000357997.10	NP_055929.1	Q86XL3-1
ANKLE2	XM_005266159.4 link	c.2430-117G>A	intron_variant	Intron 12 of 12		XP_005266216.1
ANKLE2	XM_006719735.2 link	c.2024-117G>A	intron_variant	Intron 11 of 11		XP_006719798.1
ANKLE2	XM_024448899.2 link	c.1305-117G>A	intron_variant	Intron 8 of 8		XP_024304667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKLE2	ENST00000357997.10 link	c.2616-117G>A		intron_variant	Intron 12 of 12	1	NM_015114.3	ENSP00000350686.5		Q86XL3-1

Frequencies

GnomAD3 genomes

AF:

0.197

AC:

12597

AN:

64046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.211

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.205

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.219

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.370

AC:

247884

AN:

669854

Hom.:

50012

AF XY:

0.361

AC XY:

121596

AN XY:

336432

show subpopulations

Gnomad4 AFR exome

AF:

0.323

Gnomad4 AMR exome

AF:

0.484

Gnomad4 ASJ exome

AF:

0.309

Gnomad4 EAS exome

AF:

0.384

Gnomad4 SAS exome

AF:

0.247

Gnomad4 FIN exome

AF:

0.414

Gnomad4 NFE exome

AF:

0.379

Gnomad4 OTH exome

AF:

0.327

GnomAD4 genome

AF:

0.197

AC:

12608

AN:

64112

Hom.:

Cov.:

AF XY:

0.209

AC XY:

6495

AN XY:

31070

show subpopulations

Gnomad4 AFR

AF:

0.178

Gnomad4 AMR

AF:

0.196

Gnomad4 ASJ

AF:

0.171

Gnomad4 EAS

AF:

0.211

Gnomad4 SAS

AF:

0.214

Gnomad4 FIN

AF:

0.288

Gnomad4 NFE

AF:

0.195

Gnomad4 OTH

AF:

0.214

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 17, 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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.85

DANN

Benign

0.77

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