12-132727540-G-A

Position:

• chr12-132727540-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015114.3(ANKLE2):​c.2616-97C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,373,968 control chromosomes in the GnomAD database, including 12,152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1293 hom., cov: 47)
  • Exomes 𝑓: 0.12 (10859 hom.)
• Consequence: ANKLE2 NM_015114.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.28

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 12-132727540-G-A is Benign according to our data. Variant chr12-132727540-G-A is described in ClinVar as [Benign]. Clinvar id is 1257867.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKLE2	NM_015114.3	c.2616-97C>T		intron_variant		ENST00000357997.10	NP_055929.1
ANKLE2	XM_005266159.4	c.2430-97C>T		intron_variant			XP_005266216.1
ANKLE2	XM_006719735.2	c.2024-97C>T		intron_variant			XP_006719798.1
ANKLE2	XM_024448899.2	c.1305-97C>T		intron_variant			XP_024304667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKLE2	ENST00000357997.10	c.2616-97C>T		intron_variant		1	NM_015114.3	ENSP00000350686.5

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18369 AN: 151568 Hom.: 1290 Cov.: 47

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.0856

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.00772

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.0325

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.123

GnomAD4 exome AF: 0.123 AC: 150575 AN: 1222286 Hom.: 10859 AF XY: 0.124 AC XY: 75402 AN XY: 605904

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.0823

Gnomad4 ASJ exome AF: 0.130

Gnomad4 EAS exome AF: 0.00372

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.0421

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.129

GnomAD4 genome AF: 0.121 AC: 18381 AN: 151682 Hom.: 1293 Cov.: 47 AF XY: 0.117 AC XY: 8648 AN XY: 74158

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.00794

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.0325

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.124

Alfa AF: 0.133 Hom.: 98

Bravo AF: 0.126

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 17, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.17
DANN	Benign	0.63

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: rs35235926; hg19: chr12-133304126;