12-132727581-G-A

Variant names:

• chr12-132727581-G-A
• rs868135191
• NM_015114.3:c.2616-138C>T

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.2616-138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 141,484 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (122 hom., cov: 44)
  • Exomes 𝑓: 0.00095 (27 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKLE2 NM_015114.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.473

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=-0.93).
• BP6: Variant 12-132727581-G-A is Benign according to our data. Variant chr12-132727581-G-A is described in ClinVar as [Benign]. Clinvar id is 1275725.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKLE2	NM_015114.3	c.2616-138C>T		intron_variant	Intron 12 of 12	ENST00000357997.10	NP_055929.1
ANKLE2	XM_005266159.4	c.2430-138C>T		intron_variant	Intron 12 of 12		XP_005266216.1
ANKLE2	XM_006719735.2	c.2024-138C>T		intron_variant	Intron 11 of 11		XP_006719798.1
ANKLE2	XM_024448899.2	c.1305-138C>T		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.2616-138C>T		intron_variant	Intron 12 of 12	1	NM_015114.3	ENSP00000350686.5

Frequencies

GnomAD3 genomes AF: 0.0201 AC: 2842 AN: 141416 Hom.: 122 Cov.: 44

Gnomad AFR AF: 0.0711

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00833

Gnomad ASJ AF: 0.0103

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000440

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00355

Gnomad NFE AF: 0.000464

Gnomad OTH AF: 0.0107

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000946 AC: 557 AN: 588890 Hom.: 27 AF XY: 0.000838 AC XY: 255 AN XY: 304236

Gnomad4 AFR exome AF: 0.0256

Gnomad4 AMR exome AF: 0.00225

Gnomad4 ASJ exome AF: 0.00250

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000168

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000839

Gnomad4 OTH exome AF: 0.00170

GnomAD4 genome AF: 0.0202 AC: 2858 AN: 141484 Hom.: 122 Cov.: 44 AF XY: 0.0199 AC XY: 1377 AN XY: 69070

Gnomad4 AFR AF: 0.0714

Gnomad4 AMR AF: 0.00832

Gnomad4 ASJ AF: 0.0103

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000441

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000464

Gnomad4 OTH AF: 0.0106

Alfa AF: 0.0155 Hom.: 1

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 14, 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	-0.93
CADD	Benign	4.9
DANN	Benign	0.79

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: rs868135191; hg19: chr12-133304167;