Variant 12-132727125-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015114.3(ANKLE2):c.*117G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000809 in 1,104,386 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00040 ( 4 hom. )

Consequence

ANKLE2
NM_015114.3 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.724

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 12-132727125-C-T is Benign according to our data. Variant chr12-132727125-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2507210.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
ANKLE2	NM_015114.3 link	c.*117G>A	3_prime_UTR_variant	13/13	ENST00000357997.10	NP_055929.1	Q86XL3-1
ANKLE2	XM_005266159.4 link	c.*117G>A	3_prime_UTR_variant	13/13		XP_005266216.1
ANKLE2	XM_006719735.2 link	c.*299G>A	3_prime_UTR_variant	12/12		XP_006719798.1
ANKLE2	XM_024448899.2 link	c.*117G>A	3_prime_UTR_variant	9/9		XP_024304667.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ANKLE2	ENST00000357997 link	c.*117G>A	3_prime_UTR_variant	13/13	1	NM_015114.3	ENSP00000350686.5	Q86XL3-1
ANKLE2	ENST00000542282 link	c.*117G>A	3_prime_UTR_variant	3/3	1		ENSP00000437807.1	Q86XL3-3
ANKLE2	ENST00000539605.5 link	n.9433G>A	non_coding_transcript_exon_variant	12/12	1
ANKLE2	ENST00000542657.5 link	c.*117G>A	downstream_gene_variant		2		ENSP00000438551.1	Q86XL3-3

Frequencies

GnomAD3 genomes

AF:

0.00336

AC:

512

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00239

GnomAD4 exome

AF:

0.000398

AC:

379

AN:

952022

Hom.:

Cov.:

AF XY:

0.000385

AC XY:

180

AN XY:

467280

show subpopulations

Gnomad4 AFR exome

AF:

0.0129

Gnomad4 AMR exome

AF:

0.00117

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000429

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000311

Gnomad4 OTH exome

AF:

0.00100

GnomAD4 genome

AF:

0.00338

AC:

515

AN:

152364

Hom.:

Cov.:

AF XY:

0.00340

AC XY:

253

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0120

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00133

Hom.:

Bravo

AF:

0.00394

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 31, 2019

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

6.1

DANN

Benign

0.61

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