NM_024783.4:c.2706G>A

Variant names:

• chr11-47660176-C-T
• rs143937205
• NM_024783.4:c.2706G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_024783.4(AGBL2):​c.2706G>A​(p.Pro902Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00209 in 1,609,290 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (6 hom.)
• Consequence: AGBL2 NM_024783.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -7.98
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-47660176-C-T is Benign according to our data. Variant chr11-47660176-C-T is described in ClinVar as Benign. ClinVar VariationId is 791546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-7.98 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL2	NM_024783.4	MANE Select	c.2706G>A	p.Pro902Pro	synonymous	Exon 19 of 19	NP_079059.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL2	ENST00000525123.6	TSL:1 MANE Select	c.2706G>A	p.Pro902Pro	synonymous	Exon 19 of 19	ENSP00000435582.1	Q5U5Z8-1
	AGBL2	ENST00000528609.5	TSL:1	n.*833G>A		non_coding_transcript_exon	Exon 9 of 9	ENSP00000431912.1	J9JIH1
	AGBL2	ENST00000528609.5	TSL:1	n.*833G>A		3_prime_UTR	Exon 9 of 9	ENSP00000431912.1	J9JIH1

Frequencies

GnomAD3 genomes AF: 0.00191 AC: 290 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00269

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00241 AC: 597 AN: 247386 AF XY: 0.00258

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000744

Gnomad ASJ exome AF: 0.0105

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00116

Gnomad NFE exome AF: 0.00290

Gnomad OTH exome AF: 0.00249

GnomAD4 exome AF: 0.00211 AC: 3081 AN: 1456988 Hom.: 6 Cov.: 30 AF XY: 0.00218 AC XY: 1581 AN XY: 724426

African (AFR) AF: 0.000330 AC: 11 AN: 33336

American (AMR) AF: 0.000821 AC: 36 AN: 43830

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 261 AN: 25922

East Asian (EAS) AF: 0.00 AC: 0 AN: 39600

South Asian (SAS) AF: 0.00293 AC: 250 AN: 85458

European-Finnish (FIN) AF: 0.00103 AC: 55 AN: 53372

Middle Eastern (MID) AF: 0.00966 AC: 53 AN: 5488

European-Non Finnish (NFE) AF: 0.00206 AC: 2281 AN: 1109760

Other (OTH) AF: 0.00223 AC: 134 AN: 60222

GnomAD4 genome AF: 0.00190 AC: 290 AN: 152302 Hom.: 0 Cov.: 32 AF XY: 0.00197 AC XY: 147 AN XY: 74462

African (AFR) AF: 0.000385 AC: 16 AN: 41564

American (AMR) AF: 0.00131 AC: 20 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4828

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00269 AC: 183 AN: 68032

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.00325 Hom.: 0

Bravo AF: 0.00172

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.00355

EpiControl AF: 0.00332

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.079
DANN	Benign	0.53
PhyloP100		-8.0
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs143937205; hg19: chr11-47681728; COSMIC: COSV54090577;