12-132727596-G-A

Position:

• chr12-132727596-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1271452.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKLE2	NM_015114.3	c.2616-153C>T		intron_variant		ENST00000357997.10	NP_055929.1
ANKLE2	XM_005266159.4	c.2430-153C>T		intron_variant			XP_005266216.1
ANKLE2	XM_006719735.2	c.2024-153C>T		intron_variant			XP_006719798.1
ANKLE2	XM_024448899.2	c.1305-153C>T		intron_variant			XP_024304667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKLE2	ENST00000357997.10	c.2616-153C>T		intron_variant		1	NM_015114.3	ENSP00000350686.5

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

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.175

Alfa AF: 0.412 Hom.: 1

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.86
DANN	Benign	0.60

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

LitVar

Other links and lift over

dbSNP: rs555826589; hg19: chr12-133304182;