11-47679976-C-G

Position:

• chr11-47679976-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000525123.6(AGBL2):​c.2013G>C​(p.Met671Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AGBL2 ENST00000525123.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.506

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058359742).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGBL2	NM_024783.4	c.2013G>C	p.Met671Ile	missense_variant	13/19	ENST00000525123.6	NP_079059.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGBL2	ENST00000525123.6	c.2013G>C	p.Met671Ile	missense_variant	13/19	1	NM_024783.4	ENSP00000435582	P2
AGBL2	ENST00000528609.5	c.*140G>C		3_prime_UTR_variant, NMD_transcript_variant	3/9	1		ENSP00000431912
AGBL2	ENST00000528244.5	c.1899G>C	p.Met633Ile	missense_variant	12/16	2		ENSP00000436630	A2
AGBL2	ENST00000529712.5	n.2547G>C		non_coding_transcript_exon_variant	10/11	2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1442050 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 718766

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	15
DANN	Benign	0.90
DEOGEN2	Benign	0.0031	T;.;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.19	N
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.058	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N;.;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.20	N;N;N
REVEL	Benign	0.026
Sift	Benign	0.079	T;T;T
Sift4G	Benign	0.16	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.015
MutPred		0.19		Gain of methylation at K672 (P = 0.0258);Gain of methylation at K672 (P = 0.0258);.;
MVP		0.081
MPC		0.12
ClinPred		0.18	T
GERP RS		0.55
Varity_R		0.082
gMVP		0.50

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

Other links and lift over

dbSNP: rs12286721; hg19: chr11-47701528;