rs1566007073

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• microcephaly 16, primary, autosomal recessive

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015114.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKLE2	NM_015114.3	MANE Select	c.2616-117delG		intron	N/A	NP_055929.1	Q86XL3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKLE2	ENST00000357997.10	TSL:1 MANE Select	c.2616-117delG		intron	N/A	ENSP00000350686.5	Q86XL3-1
	ANKLE2	ENST00000542282.5	TSL:1	c.681-117delG		intron	N/A	ENSP00000437807.1	Q86XL3-3
	ANKLE2	ENST00000539605.5	TSL:1	n.9115-117delG		intron	N/A

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

African (AFR) AF: 0.0211 AC: 488 AN: 23132

American (AMR) AF: 0.0197 AC: 593 AN: 30174

Ashkenazi Jewish (ASJ) AF: 0.0184 AC: 325 AN: 17656

East Asian (EAS) AF: 0.00676 AC: 203 AN: 30008

South Asian (SAS) AF: 0.0143 AC: 848 AN: 59452

European-Finnish (FIN) AF: 0.0220 AC: 749 AN: 34086

Middle Eastern (MID) AF: 0.0761 AC: 335 AN: 4400

European-Non Finnish (NFE) AF: 0.0242 AC: 17326 AN: 717206

Other (OTH) AF: 0.0192 AC: 799 AN: 41544

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

African (AFR) AF: 0.0287 AC: 1146 AN: 39888

American (AMR) AF: 0.0302 AC: 450 AN: 14910

Ashkenazi Jewish (ASJ) AF: 0.0302 AC: 103 AN: 3406

East Asian (EAS) AF: 0.0433 AC: 214 AN: 4938

South Asian (SAS) AF: 0.0350 AC: 165 AN: 4712

European-Finnish (FIN) AF: 0.0575 AC: 579 AN: 10072

Middle Eastern (MID) AF: 0.0643 AC: 18 AN: 280

European-Non Finnish (NFE) AF: 0.0299 AC: 1993 AN: 66700

Other (OTH) AF: 0.0321 AC: 66 AN: 2054

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1566007073; hg19: chr12-133304145;