NM_024783.4:c.2159C>T

Variant names:

• chr11-47668896-G-A
• rs1394855172
• NM_024783.4:c.2159C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024783.4(AGBL2):​c.2159C>T​(p.Ser720Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AGBL2 NM_024783.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.96
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4021718).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024783.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL2	NM_024783.4	MANE Select	c.2159C>T	p.Ser720Phe	missense	Exon 15 of 19	NP_079059.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL2	ENST00000525123.6	TSL:1 MANE Select	c.2159C>T	p.Ser720Phe	missense	Exon 15 of 19	ENSP00000435582.1	Q5U5Z8-1
	AGBL2	ENST00000528244.5	TSL:2	c.2045C>T	p.Ser682Phe	missense	Exon 14 of 16	ENSP00000436630.1	F6U0I4
	AGBL2	ENST00000528609.5	TSL:1	n.*286C>T		non_coding_transcript_exon	Exon 5 of 9	ENSP00000431912.1	J9JIH1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460724 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726746

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111302

Other (OTH) AF: 0.0000166 AC: 1 AN: 60344

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.0
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.21
Sift	Uncertain	0.015	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.47
MutPred		0.17		Loss of phosphorylation at S720 (P = 0.0039)
MVP		0.58
MPC		0.56
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.57
gMVP		0.39
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1394855172; hg19: chr11-47690448;