12-132727031-A-T

Position:

• chr12-132727031-A-T

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.*211T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 596,184 control chromosomes in the GnomAD database, including 403 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (283 hom., cov: 33)
  • Exomes 𝑓: 0.0053 (120 hom.)
• Consequence: ANKLE2 NM_015114.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0660

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=-0.57).
• BP6: Variant 12-132727031-A-T is Benign according to our data. Variant chr12-132727031-A-T is described in ClinVar as [Benign]. Clinvar id is 1226830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKLE2	NM_015114.3	c.*211T>A		3_prime_UTR_variant	13/13	ENST00000357997.10	NP_055929.1
ANKLE2	XM_005266159.4	c.*211T>A		3_prime_UTR_variant	13/13		XP_005266216.1
ANKLE2	XM_006719735.2	c.*393T>A		3_prime_UTR_variant	12/12		XP_006719798.1
ANKLE2	XM_024448899.2	c.*211T>A		3_prime_UTR_variant	9/9		XP_024304667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKLE2	ENST00000357997	c.*211T>A		3_prime_UTR_variant	13/13	1	NM_015114.3	ENSP00000350686.5
ANKLE2	ENST00000542282	c.*211T>A		3_prime_UTR_variant	3/3	1		ENSP00000437807.1
ANKLE2	ENST00000539605.5	n.9527T>A		non_coding_transcript_exon_variant	12/12	1

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 5308 AN: 152216 Hom.: 274 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000764

Gnomad OTH AF: 0.0229

GnomAD4 exome AF: 0.00534 AC: 2371 AN: 443850 Hom.: 120 Cov.: 6 AF XY: 0.00475 AC XY: 1071 AN XY: 225656

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.0114

Gnomad4 ASJ exome AF: 0.0116

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000434

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000742

Gnomad4 OTH exome AF: 0.0122

GnomAD4 genome AF: 0.0351 AC: 5353 AN: 152334 Hom.: 283 Cov.: 33 AF XY: 0.0343 AC XY: 2552 AN XY: 74488

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0151

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000764

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0213 Hom.: 23

Bravo AF: 0.0408

Asia WGS AF: 0.0100 AC: 36 AN: 3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	4.2
DANN	Benign	0.91

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: rs11834753; hg19: chr12-133303617;