Genetic Variant NM_015114.3:c.2616-117delG (chr12-132727559-AC-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.27

Publications

0 publications found

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 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

ANKLE2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	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.:

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

711

1423

2134

2846

3557

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

764

1528

2292

3056

3820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0323

AC:

4771

AN:

147846

Hom.:

Cov.:

AF XY:

0.0321

AC XY:

2320

AN XY:

72266

show subpopulations

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:

AN:

280

European-Non Finnish (NFE)

AF:

0.0299

AC:

1993

AN:

66700

Other (OTH)

AF:

0.0321

AC:

AN:

2054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

142

284

427

569

711

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over