Genetic Variant NM_024783.4:c.2013G>A (chr11-47679976-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024783.4(AGBL2):c.2013G>A(p.Met671Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.0 ( 0 hom., cov: 29)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AGBL2
NM_024783.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.506

Publications

50 publications found

Variant links:

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

AGBL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.058587223).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL2	NM_024783.4	MANE Select	c.2013G>A	p.Met671Ile	missense	Exon 13 of 19	NP_079059.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AGBL2	ENST00000525123.6	TSL:1 MANE Select	c.2013G>A	p.Met671Ile	missense	Exon 13 of 19	ENSP00000435582.1
AGBL2	ENST00000528244.5	TSL:2	c.1899G>A	p.Met633Ile	missense	Exon 12 of 16	ENSP00000436630.1
AGBL2	ENST00000528609.5	TSL:1	n.*140G>A		non_coding_transcript_exon	Exon 3 of 9	ENSP00000431912.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151326

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.93e-7

AC:

AN:

1442046

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718764

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32882

American (AMR)

AF:

0.00

AC:

AN:

44266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25928

East Asian (EAS)

AF:

0.00

AC:

AN:

39532

South Asian (SAS)

AF:

0.00

AC:

AN:

85520

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53266

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

9.13e-7

AC:

AN:

1095338

Other (OTH)

AF:

0.00

AC:

AN:

59606

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151326

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73828

African (AFR)

AF:

0.00

AC:

AN:

41154

American (AMR)

AF:

0.00

AC:

AN:

15150

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10444

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67840

Other (OTH)

AF:

0.00

AC:

AN:

2084

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0031

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.46

M_CAP

Benign

0.0022

MetaRNN

Benign

0.059

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

PhyloP100

0.51

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.20

REVEL

Benign

0.026

Sift

Benign

0.079

Sift4G

Benign

0.16

Polyphen

0.0

Vest4

0.015

MutPred

0.19

Gain of methylation at K672 (P = 0.0258)

MVP

0.081

MPC

0.12

ClinPred

0.18

GERP RS

0.55

Varity_R

0.082

gMVP

0.50

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over