rs34136118

Variant names:

• chr11-47660326-T-C
• rs34136118
• NM_024783.4:c.2556A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_024783.4(AGBL2):​c.2556A>G​(p.Thr852Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,612,282 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0079 (16 hom., cov: 32)
  • Exomes 𝑓: 0.00081 (14 hom.)
• Consequence: AGBL2 NM_024783.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.102
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-47660326-T-C is Benign according to our data. Variant chr11-47660326-T-C is described in ClinVar as Benign. ClinVar VariationId is 779198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.102 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00792 (1206/152358) while in subpopulation AFR AF = 0.0269 (1119/41580). AF 95% confidence interval is 0.0256. There are 16 homozygotes in GnomAd4. There are 553 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 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.2556A>G	p.Thr852Thr	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.2556A>G	p.Thr852Thr	synonymous	Exon 19 of 19	ENSP00000435582.1	Q5U5Z8-1
	AGBL2	ENST00000528609.5	TSL:1	n.*683A>G		non_coding_transcript_exon	Exon 9 of 9	ENSP00000431912.1	J9JIH1
	AGBL2	ENST00000528609.5	TSL:1	n.*683A>G		3_prime_UTR	Exon 9 of 9	ENSP00000431912.1	J9JIH1

Frequencies

GnomAD3 genomes AF: 0.00793 AC: 1208 AN: 152240 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.0270

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00367

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00812

GnomAD2 exomes AF: 0.00222 AC: 550 AN: 247492 AF XY: 0.00171

Gnomad AFR exome AF: 0.0281

Gnomad AMR exome AF: 0.00207

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000142

Gnomad OTH exome AF: 0.00167

GnomAD4 exome AF: 0.000807 AC: 1178 AN: 1459924 Hom.: 14 Cov.: 30 AF XY: 0.000697 AC XY: 506 AN XY: 726326

African (AFR) AF: 0.0263 AC: 876 AN: 33362

American (AMR) AF: 0.00214 AC: 94 AN: 44002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26066

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85908

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53398

Middle Eastern (MID) AF: 0.000869 AC: 5 AN: 5756

European-Non Finnish (NFE) AF: 0.0000810 AC: 90 AN: 1111464

Other (OTH) AF: 0.00182 AC: 110 AN: 60300

GnomAD4 genome AF: 0.00792 AC: 1206 AN: 152358 Hom.: 16 Cov.: 32 AF XY: 0.00742 AC XY: 553 AN XY: 74510

African (AFR) AF: 0.0269 AC: 1119 AN: 41580

American (AMR) AF: 0.00366 AC: 56 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68044

Other (OTH) AF: 0.00803 AC: 17 AN: 2116

Alfa AF: 0.00296 Hom.: 14

Bravo AF: 0.00915

Asia WGS AF: 0.00346 AC: 12 AN: 3478

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	-0.86
CADD	Benign	5.7
DANN	Benign	0.49
PhyloP100		0.10
Mutation Taster		=100/0	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: rs34136118; hg19: chr11-47681878;