12-132734557-CAG-TAA

Variant names:

• chr12-132734557-CAG-TAA
• NM_015114.3:c.1717_1719delCTGinsTTA
• ANKLE2 p.574

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015114.3(ANKLE2):​c.1717_1719delCTGinsTTA​(p.574) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANKLE2 NM_015114.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.14
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.1717_1719delCTGinsTTA	p.574	synonymous	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.1717_1719delCTGinsTTA	p.574	synonymous	N/A	ENSP00000350686.5	Q86XL3-1
	ANKLE2	ENST00000539605.5	TSL:1	n.8216_8218delCTGinsTTA		non_coding_transcript_exon	Exon 9 of 12
	ANKLE2	ENST00000538766.1	TSL:2	c.-219_-217delCTGinsTTA		5_prime_UTR	Exon 1 of 4	ENSP00000445760.1	F5H1D4

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-133311143;