12-132727559-AC-A

Variant names:

• chr12-132727559-AC-A
• rs1566007073
• NM_015114.3:c.2616-117delG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015114.3(ANKLE2):​c.2616-117delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0239 in 1,105,504 control chromosomes in the GnomAD database, including 2,126 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.032 (83 hom., cov: 0)
  • Exomes 𝑓: 0.023 (2043 hom.)
• Consequence: ANKLE2 NM_015114.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.27

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 -10 ACMG points.

• BP6: Variant 12-132727559-AC-A is Benign according to our data. Variant chr12-132727559-AC-A is described in ClinVar as [Benign]. Clinvar id is 1289205.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKLE2	NM_015114.3	c.2616-117delG		intron_variant	Intron 12 of 12	ENST00000357997.10	NP_055929.1
ANKLE2	XM_005266159.4	c.2430-117delG		intron_variant	Intron 12 of 12		XP_005266216.1
ANKLE2	XM_006719735.2	c.2024-117delG		intron_variant	Intron 11 of 11		XP_006719798.1
ANKLE2	XM_024448899.2	c.1305-117delG		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	c.2616-117delG		intron_variant	Intron 12 of 12	1	NM_015114.3	ENSP00000350686.5

Frequencies

GnomAD3 genomes AF: 0.0322 AC: 4757 AN: 147746 Hom.: 83 Cov.: 0

Gnomad AFR AF: 0.0284

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.0301

Gnomad ASJ AF: 0.0302

Gnomad EAS AF: 0.0438

Gnomad SAS AF: 0.0344

Gnomad FIN AF: 0.0575

Gnomad MID AF: 0.0671

Gnomad NFE AF: 0.0299

Gnomad OTH AF: 0.0319

GnomAD4 exome AF: 0.0226 AC: 21666 AN: 957658 Hom.: 2043 AF XY: 0.0220 AC XY: 10567 AN XY: 480030

Gnomad4 AFR exome AF: 0.0211

Gnomad4 AMR exome AF: 0.0197

Gnomad4 ASJ exome AF: 0.0184

Gnomad4 EAS exome AF: 0.00676

Gnomad4 SAS exome AF: 0.0143

Gnomad4 FIN exome AF: 0.0220

Gnomad4 NFE exome AF: 0.0242

Gnomad4 OTH exome AF: 0.0192

GnomAD4 genome AF: 0.0323 AC: 4771 AN: 147846 Hom.: 83 Cov.: 0 AF XY: 0.0321 AC XY: 2320 AN XY: 72266

Gnomad4 AFR AF: 0.0287

Gnomad4 AMR AF: 0.0302

Gnomad4 ASJ AF: 0.0302

Gnomad4 EAS AF: 0.0433

Gnomad4 SAS AF: 0.0350

Gnomad4 FIN AF: 0.0575

Gnomad4 NFE AF: 0.0299

Gnomad4 OTH AF: 0.0321

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 27, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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: rs1566007073; hg19: chr12-133304145;