NM_015114.3:c.*211T>A

Variant names:

• chr12-132727031-A-T
• rs11834753
• NM_015114.3:c.*211T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015114.3(ANKLE2):​c.*211T>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 0.013 in 596,184 control chromosomes in the GnomAD database, including 403 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (283 hom., cov: 33)
  • Exomes 𝑓: 0.0053 (120 hom.)
• Consequence: ANKLE2 NM_015114.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0660
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 12-132727031-A-T is Benign according to our data. Variant chr12-132727031-A-T is described in ClinVar as Benign. ClinVar VariationId is 1226830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 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.*211T>A		3_prime_UTR	Exon 13 of 13	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.*211T>A		3_prime_UTR	Exon 13 of 13	ENSP00000350686.5	Q86XL3-1
	ANKLE2	ENST00000542282.5	TSL:1	c.*211T>A		3_prime_UTR	Exon 3 of 3	ENSP00000437807.1	Q86XL3-3
	ANKLE2	ENST00000539605.5	TSL:1	n.9527T>A		non_coding_transcript_exon	Exon 12 of 12

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 5308 AN: 152216 Hom.: 274 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000764

Gnomad OTH AF: 0.0229

GnomAD4 exome AF: 0.00534 AC: 2371 AN: 443850 Hom.: 120 Cov.: 6 AF XY: 0.00475 AC XY: 1071 AN XY: 225656

African (AFR) AF: 0.122 AC: 1503 AN: 12334

American (AMR) AF: 0.0114 AC: 168 AN: 14766

Ashkenazi Jewish (ASJ) AF: 0.0116 AC: 144 AN: 12376

East Asian (EAS) AF: 0.00 AC: 0 AN: 28916

South Asian (SAS) AF: 0.000434 AC: 11 AN: 25324

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25948

Middle Eastern (MID) AF: 0.0131 AC: 24 AN: 1826

European-Non Finnish (NFE) AF: 0.000742 AC: 221 AN: 297694

Other (OTH) AF: 0.0122 AC: 300 AN: 24666

GnomAD4 genome AF: 0.0351 AC: 5353 AN: 152334 Hom.: 283 Cov.: 33 AF XY: 0.0343 AC XY: 2552 AN XY: 74488

African (AFR) AF: 0.120 AC: 4970 AN: 41550

American (AMR) AF: 0.0151 AC: 231 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 44 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000764 AC: 52 AN: 68032

Other (OTH) AF: 0.0227 AC: 48 AN: 2116

Alfa AF: 0.0213 Hom.: 23

Bravo AF: 0.0408

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	4.2
DANN	Benign	0.91
PhyloP100		0.066
Mutation Taster		=100/0	polymorphism (auto)

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: rs11834753; hg19: chr12-133303617;