NM_024783.4:c.1747C>G

Variant names:

• chr11-47685934-G-C
• NM_024783.4:c.1747C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_024783.4(AGBL2):​c.1747C>G​(p.Arg583Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AGBL2 NM_024783.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.45

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.796

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL2	NM_024783.4	c.1747C>G	p.Arg583Gly	missense_variant	Exon 11 of 19	ENST00000525123.6	NP_079059.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL2	ENST00000525123.6	c.1747C>G	p.Arg583Gly	missense_variant	Exon 11 of 19	1	NM_024783.4	ENSP00000435582.1
AGBL2	ENST00000528244.5	c.1633C>G	p.Arg545Gly	missense_variant	Exon 10 of 16	2		ENSP00000436630.1
AGBL2	ENST00000528609.5	n.294-3839C>G		intron_variant	Intron 1 of 8	1		ENSP00000431912.1
AGBL2	ENST00000529712.5	n.2281C>G		non_coding_transcript_exon_variant	Exon 8 of 11	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461768 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727198

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.064	D
MetaRNN	Pathogenic	0.80	D;D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Pathogenic	3.6	H;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-6.7	D;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.011	D;D;D
Sift4G	Uncertain	0.016	D;D;D
Polyphen		0.80	P;.;D
Vest4		0.90
MutPred		0.63		Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);.;
MVP		0.59
MPC		0.61
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.65
gMVP		0.95

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: chr11-47707486;