Variant chr11-47667662-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024783.4(AGBL2):c.2249A>T(p.Lys750Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,758 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: 0.0000014 ( 0 hom. )

Consequence

AGBL2
NM_024783.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.82

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24914953).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGBL2	NM_024783.4 link	c.2249A>T	p.Lys750Ile	missense_variant	16/19	ENST00000525123.6	NP_079059.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AGBL2	ENST00000525123.6 link	c.2249A>T	p.Lys750Ile	missense_variant	16/19	1	NM_024783.4	ENSP00000435582.1	Q5U5Z8-1
AGBL2	ENST00000528244.5 link	c.2135A>T	p.Lys712Ile	missense_variant	15/16	2		ENSP00000436630.1	F6U0I4
AGBL2	ENST00000528609.5 link	n.*376A>T		non_coding_transcript_exon_variant	6/9	1		ENSP00000431912.1	J9JIH1
AGBL2	ENST00000528609.5 link	n.*376A>T		3_prime_UTR_variant	6/9	1		ENSP00000431912.1	J9JIH1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250130

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135308

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000876

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460758

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726772

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2022

The c.2249A>T (p.K750I) alteration is located in exon 16 (coding exon 15) of the AGBL2 gene. This alteration results from a A to T substitution at nucleotide position 2249, causing the lysine (K) at amino acid position 750 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;.;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.94

M_CAP

Benign

0.015

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.8

L;.;.

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.9

D;D;D

REVEL

Benign

0.087

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.45

MutPred

0.21

Loss of methylation at K750 (P = 0.0208);.;.;

MVP

0.44

MPC

0.67

ClinPred

0.94

GERP RS

4.3

Varity_R

0.31

gMVP

0.15

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over