rs12286721

Variant names:

• chr11-47679976-C-A
• rs12286721
• NM_024783.4:c.2013G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-47679976-C-A
• chr11-47679976-C-G
• chr11-47679976-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024783.4(AGBL2):​c.2013G>T​(p.Met671Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 1,587,002 control chromosomes in the GnomAD database, including 253,138 homozygotes. 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.

• Frequency:
  • Genomes: 𝑓 0.59 (27002 hom., cov: 29)
  • Exomes 𝑓: 0.56 (226136 hom.)
• Consequence: AGBL2 NM_024783.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.506
• Publications: 50 publications found

Genes affected

AGBL2 (HGNC:26296): (AGBL carboxypeptidase 2) Predicted to enable metallocarboxypeptidase activity. Predicted to be involved in protein side chain deglutamylation. Located in centriole and ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

AGBL2 Gene-Disease associations (from GenCC):

• epilepsy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.6918674E-6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL2	NM_024783.4	c.2013G>T	p.Met671Ile	missense_variant	Exon 13 of 19	ENST00000525123.6	NP_079059.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL2	ENST00000525123.6	c.2013G>T	p.Met671Ile	missense_variant	Exon 13 of 19	1	NM_024783.4	ENSP00000435582.1
AGBL2	ENST00000528244.5	c.1899G>T	p.Met633Ile	missense_variant	Exon 12 of 16	2		ENSP00000436630.1

Frequencies

GnomAD3 genomes AF: 0.594 AC: 89788 AN: 151222 Hom.: 26979 Cov.: 29

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.559

GnomAD2 exomes AF: 0.581 AC: 144818 AN: 249432 AF XY: 0.568

Gnomad AFR exome AF: 0.629

Gnomad AMR exome AF: 0.738

Gnomad ASJ exome AF: 0.508

Gnomad EAS exome AF: 0.609

Gnomad FIN exome AF: 0.657

Gnomad NFE exome AF: 0.547

Gnomad OTH exome AF: 0.563

GnomAD4 exome AF: 0.557 AC: 799242 AN: 1435662 Hom.: 226136 Cov.: 26 AF XY: 0.553 AC XY: 395936 AN XY: 715812

African (AFR) AF: 0.639 AC: 20923 AN: 32744

American (AMR) AF: 0.727 AC: 32146 AN: 44204

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 12953 AN: 25858

East Asian (EAS) AF: 0.676 AC: 26666 AN: 39472

South Asian (SAS) AF: 0.465 AC: 39707 AN: 85354

European-Finnish (FIN) AF: 0.647 AC: 34425 AN: 53212

Middle Eastern (MID) AF: 0.545 AC: 3103 AN: 5696

European-Non Finnish (NFE) AF: 0.547 AC: 596459 AN: 1089740

Other (OTH) AF: 0.553 AC: 32860 AN: 59382

GnomAD4 genome AF: 0.594 AC: 89850 AN: 151340 Hom.: 27002 Cov.: 29 AF XY: 0.600 AC XY: 44315 AN XY: 73894

African (AFR) AF: 0.636 AC: 26242 AN: 41238

American (AMR) AF: 0.654 AC: 9911 AN: 15152

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1749 AN: 3466

East Asian (EAS) AF: 0.614 AC: 3158 AN: 5146

South Asian (SAS) AF: 0.478 AC: 2294 AN: 4798

European-Finnish (FIN) AF: 0.666 AC: 6946 AN: 10430

Middle Eastern (MID) AF: 0.627 AC: 183 AN: 292

European-Non Finnish (NFE) AF: 0.553 AC: 37504 AN: 67802

Other (OTH) AF: 0.563 AC: 1186 AN: 2106

Alfa AF: 0.558 Hom.: 82415

Bravo AF: 0.599

TwinsUK AF: 0.551 AC: 2044

ALSPAC AF: 0.556 AC: 2143

ESP6500AA AF: 0.615 AC: 2709

ESP6500EA AF: 0.546 AC: 4694

ExAC AF: 0.572 AC: 69399

Asia WGS AF: 0.511 AC: 1779 AN: 3478

EpiCase AF: 0.543

EpiControl AF: 0.529

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	16
DANN	Benign	0.88
DEOGEN2	Benign	0.0031	T;.;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.53	D
MetaRNN	Benign	0.0000027	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N;.;.
PhyloP100		0.51
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.20	N;N;N
REVEL	Benign	0.036
Sift	Benign	0.079	T;T;T
Sift4G	Benign	0.16	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.015
MutPred		0.19		Gain of methylation at K672 (P = 0.0258);Gain of methylation at K672 (P = 0.0258);.;
MPC		0.12
ClinPred		0.0046	T
GERP RS		0.55
Varity_R		0.082
gMVP		0.50
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12286721; hg19: chr11-47701528; COSMIC: COSV54092398;