12-132727587-C-T

Variant names:

• chr12-132727587-C-T
• rs10437914
• NM_015114.3:c.2616-144G>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.2616-144G>A 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 0.18 (20 hom., cov: 0)
  • Exomes 𝑓: 0.22 (6856 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKLE2 NM_015114.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.196

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=-0.89).
• BP6: Variant 12-132727587-C-T is Benign according to our data. Variant chr12-132727587-C-T is described in ClinVar as [Benign]. Clinvar id is 1240707.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKLE2	NM_015114.3	c.2616-144G>A		intron_variant	Intron 12 of 12	ENST00000357997.10	NP_055929.1
ANKLE2	XM_005266159.4	c.2430-144G>A		intron_variant	Intron 12 of 12		XP_005266216.1
ANKLE2	XM_006719735.2	c.2024-144G>A		intron_variant	Intron 11 of 11		XP_006719798.1
ANKLE2	XM_024448899.2	c.1305-144G>A		intron_variant	Intron 8 of 8		XP_024304667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKLE2	ENST00000357997.10	c.2616-144G>A		intron_variant	Intron 12 of 12	1	NM_015114.3	ENSP00000350686.5

Frequencies

GnomAD3 genomes AF: 0.181 AC: 11177 AN: 61784 Hom.: 20 Cov.: 0

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.167

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.191

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.219 AC: 85968 AN: 391876 Hom.: 6856 AF XY: 0.219 AC XY: 44783 AN XY: 204306

Gnomad4 AFR exome AF: 0.192

Gnomad4 AMR exome AF: 0.369

Gnomad4 ASJ exome AF: 0.202

Gnomad4 EAS exome AF: 0.346

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.212

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.181 AC: 11185 AN: 61858 Hom.: 20 Cov.: 0 AF XY: 0.192 AC XY: 5744 AN XY: 29888

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.186

Alfa AF: 0.360 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.50
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10437914; hg19: chr12-133304173; COSMIC: COSV63294610; COSMIC: COSV63294610;