11-47679976-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024783.4(AGBL2):​c.2013G>C​(p.Met671Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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: not found (cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058359742).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1442050 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 718766

African (AFR) AF: 0.00 AC: 0 AN: 32882

American (AMR) AF: 0.00 AC: 0 AN: 44266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25928

East Asian (EAS) AF: 0.00 AC: 0 AN: 39532

South Asian (SAS) AF: 0.00 AC: 0 AN: 85520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095342

Other (OTH) AF: 0.00 AC: 0 AN: 59606

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 82415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	15
DANN	Benign	0.90
DEOGEN2	Benign	0.0031	T;.;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.19	N
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.058	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	0.026
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);.;
MVP		0.081
MPC		0.12
ClinPred		0.18	T
GERP RS		0.55
Varity_R		0.082
gMVP		0.50
Mutation Taster		=94/6	polymorphism

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;