chr11-47677295-A-T

Position:

• chr11-47677295-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024783.4(AGBL2):​c.2123T>A​(p.Ile708Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: AGBL2 NM_024783.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.08

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28638205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGBL2	NM_024783.4	c.2123T>A	p.Ile708Asn	missense_variant	14/19	ENST00000525123.6	NP_079059.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGBL2	ENST00000525123.6	c.2123T>A	p.Ile708Asn	missense_variant	14/19	1	NM_024783.4	ENSP00000435582.1
AGBL2	ENST00000528244.5	c.2009T>A	p.Ile670Asn	missense_variant	13/16	2		ENSP00000436630.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 30, 2021

The c.2123T>A (p.I708N) alteration is located in exon 14 (coding exon 13) of the AGBL2 gene. This alteration results from a T to A substitution at nucleotide position 2123, causing the isoleucine (I) at amino acid position 708 to be replaced by an asparagine (N). 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	Uncertain	0.35
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.061	T;.;.
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.97	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Benign	0.17
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.052	T;D;T
Polyphen		1.0	D;.;D
Vest4		0.35
MutPred		0.26		Loss of stability (P = 0.0396);Loss of stability (P = 0.0396);.;
MVP		0.58
MPC		0.67
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.55
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-47698847;