NM_015114.3:c.2616-153C>T

Variant names:

• chr12-132727596-G-A
• rs555826589
• NM_015114.3:c.2616-153C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_015114.3(ANKLE2):​c.2616-153C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (6 hom., cov: 0)
• Consequence: ANKLE2 NM_015114.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.100
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 12-132727596-G-A is Benign according to our data. Variant chr12-132727596-G-A is described in ClinVar as Benign. ClinVar VariationId is 1271452.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

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.2616-153C>T		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.2616-153C>T		intron	N/A	ENSP00000350686.5	Q86XL3-1
	ANKLE2	ENST00000542282.5	TSL:1	c.681-153C>T		intron	N/A	ENSP00000437807.1	Q86XL3-3
	ANKLE2	ENST00000539605.5	TSL:1	n.9115-153C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.173 AC: 10657 AN: 61766 Hom.: 6 Cov.: 0

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.141

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.179

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.173 AC: 10666 AN: 61828 Hom.: 6 Cov.: 0 AF XY: 0.183 AC XY: 5453 AN XY: 29734

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.149 AC: 2849 AN: 19112

American (AMR) AF: 0.178 AC: 1004 AN: 5656

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 193 AN: 1214

East Asian (EAS) AF: 0.203 AC: 327 AN: 1612

South Asian (SAS) AF: 0.204 AC: 437 AN: 2146

European-Finnish (FIN) AF: 0.260 AC: 922 AN: 3540

Middle Eastern (MID) AF: 0.140 AC: 16 AN: 114

European-Non Finnish (NFE) AF: 0.172 AC: 4698 AN: 27282

Other (OTH) AF: 0.175 AC: 139 AN: 796

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.412 Hom.: 1

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
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.86
DANN	Benign	0.60
PhyloP100		-0.10
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: rs555826589; hg19: chr12-133304182;