chr12-132727017-C-T

Position:

• chr12-132727017-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015114.3(ANKLE2):​c.*225G>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 0.039 in 564,622 control chromosomes in the GnomAD database, including 580 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (131 hom., cov: 33)
  • Exomes 𝑓: 0.041 (449 hom.)
• Consequence: ANKLE2 NM_015114.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.636

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 12-132727017-C-T is Benign according to our data. Variant chr12-132727017-C-T is described in ClinVar as [Benign]. Clinvar id is 1230593.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKLE2	NM_015114.3	c.*225G>A		3_prime_UTR_variant	13/13	ENST00000357997.10	NP_055929.1
ANKLE2	XM_005266159.4	c.*225G>A		3_prime_UTR_variant	13/13		XP_005266216.1
ANKLE2	XM_006719735.2	c.*407G>A		3_prime_UTR_variant	12/12		XP_006719798.1
ANKLE2	XM_024448899.2	c.*225G>A		3_prime_UTR_variant	9/9		XP_024304667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKLE2	ENST00000357997	c.*225G>A		3_prime_UTR_variant	13/13	1	NM_015114.3	ENSP00000350686.5
ANKLE2	ENST00000542282	c.*225G>A		3_prime_UTR_variant	3/3	1		ENSP00000437807.1
ANKLE2	ENST00000539605.5	n.9541G>A		non_coding_transcript_exon_variant	12/12	1

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 5254 AN: 152156 Hom.: 130 Cov.: 33

Gnomad AFR AF: 0.00929

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0404

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00496

Gnomad FIN AF: 0.0484

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0517

Gnomad OTH AF: 0.0254

GnomAD4 exome AF: 0.0407 AC: 16789 AN: 412348 Hom.: 449 Cov.: 6 AF XY: 0.0399 AC XY: 8412 AN XY: 210822

Gnomad4 AFR exome AF: 0.00706

Gnomad4 AMR exome AF: 0.0282

Gnomad4 ASJ exome AF: 0.0352

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00505

Gnomad4 FIN exome AF: 0.0447

Gnomad4 NFE exome AF: 0.0511

Gnomad4 OTH exome AF: 0.0371

GnomAD4 genome AF: 0.0345 AC: 5255 AN: 152274 Hom.: 131 Cov.: 33 AF XY: 0.0337 AC XY: 2507 AN XY: 74444

Gnomad4 AFR AF: 0.00926

Gnomad4 AMR AF: 0.0405

Gnomad4 ASJ AF: 0.0415

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00496

Gnomad4 FIN AF: 0.0484

Gnomad4 NFE AF: 0.0517

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0461 Hom.: 41

Bravo AF: 0.0311

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.27
DANN	Benign	0.70

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

Other links and lift over

dbSNP: rs74888680; hg19: chr12-133303603;