11-47690661-C-G

Variant names:

• chr11-47690661-C-G
• rs7941404
• NM_024783.4:c.1046G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000525123.6(AGBL2):​c.1046G>C​(p.Arg349Pro) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R349C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: AGBL2 ENST00000525123.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18818218).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000525123.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL2	NM_024783.4	MANE Select	c.1046G>C	p.Arg349Pro	missense	Exon 10 of 19	NP_079059.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL2	ENST00000525123.6	TSL:1 MANE Select	c.1046G>C	p.Arg349Pro	missense	Exon 10 of 19	ENSP00000435582.1
	AGBL2	ENST00000528244.5	TSL:2	c.932G>C	p.Arg311Pro	missense	Exon 9 of 16	ENSP00000436630.1
	AGBL2	ENST00000532595.5	TSL:2	c.878G>C	p.Arg293Pro	missense	Exon 8 of 8	ENSP00000436063.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	10
DANN	Benign	0.88
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.12	N
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.77	N
PhyloP100		-0.37
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.088
Sift	Benign	0.089	T
Sift4G	Benign	0.32	T
Polyphen		0.76	P
Vest4		0.18
MutPred		0.51		Loss of catalytic residue at R349 (P = 0.0121)
MVP		0.28
MPC		0.33
ClinPred		0.45	T
GERP RS		-0.36
Varity_R		0.32
gMVP		0.51
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: rs7941404; hg19: chr11-47712213;