rs77646743

Variant names:

• chr12-132727387-C-A
• NM_015114.3:c.2672G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-132727387-C-A
• chr12-132727387-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015114.3(ANKLE2):​c.2672G>T​(p.Gly891Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,408,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G891A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ANKLE2 NM_015114.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.599

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07695365).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKLE2	NM_015114.3	c.2672G>T	p.Gly891Val	missense_variant	Exon 13 of 13	ENST00000357997.10	NP_055929.1
ANKLE2	XM_005266159.4	c.2486G>T	p.Gly829Val	missense_variant	Exon 13 of 13		XP_005266216.1
ANKLE2	XM_024448899.2	c.1361G>T	p.Gly454Val	missense_variant	Exon 9 of 9		XP_024304667.1
ANKLE2	XM_006719735.2	c.*37G>T		3_prime_UTR_variant	Exon 12 of 12		XP_006719798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKLE2	ENST00000357997.10	c.2672G>T	p.Gly891Val	missense_variant	Exon 13 of 13	1	NM_015114.3	ENSP00000350686.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1408676 Hom.: 0 Cov.: 32 AF XY: 0.00000287 AC XY: 2 AN XY: 695670

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000270

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.22e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.7
DANN	Benign	0.79
DEOGEN2	Benign	0.0087	T;.;.;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.66	T;.;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.077	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.;.;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Benign	0.033
Sift	Benign	0.17	T;T;T;T
Sift4G	Benign	0.14	T;T;T;T
Polyphen		0.70	P;.;.;.
Vest4		0.048
MutPred		0.14		Loss of glycosylation at S890 (P = 0.034);.;.;.;
MVP		0.15
MPC		0.12
ClinPred		0.12	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.036
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-133303973;