chr2-27053100-T-TC

Variant names:

• chr2-27053100-T-TC
• rs1286076992
• NM_021831.6:c.143dupC

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_021831.6(AGBL5):​c.143dupC​(p.Ser49PhefsTer3) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AGBL5 NM_021831.6 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.14
• Publications: 0 publications found

Genes affected

AGBL5 (HGNC:26147): (AGBL carboxypeptidase 5) This gene encodes a metallocarboxypeptidase involved in protein deglutamylation and a member of the peptidase M14 family of proteins. The encoded protein has been described as a "dual-functional" deglutamylase that can remove glutamate residues from both carboxyl termini and side chains of protein substrates. This deglutamylase activity may be important in antiviral immunity. Mutations in this gene are associated with retinitis pigmentosa. [provided by RefSeq, Jul 2016]

AGBL5 Gene-Disease associations (from GenCC):

• inherited retinal dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 75

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-27053100-T-TC is Pathogenic according to our data. Variant chr2-27053100-T-TC is described in ClinVar as Pathogenic. ClinVar VariationId is 1391360.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021831.6. 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
	AGBL5	NM_021831.6	MANE Select	c.143dupC	p.Ser49PhefsTer3	frameshift	Exon 2 of 15	NP_068603.4
	AGBL5	NM_001035507.3		c.143dupC	p.Ser49PhefsTer3	frameshift	Exon 2 of 11	NP_001030584.1	Q8NDL9-3
	AGBL5	NR_104246.2		n.315dupC		non_coding_transcript_exon	Exon 2 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL5	ENST00000360131.5	TSL:1 MANE Select	c.143dupC	p.Ser49PhefsTer3	frameshift	Exon 2 of 15	ENSP00000353249.4	Q8NDL9-1
	AGBL5	ENST00000323064.12	TSL:1	c.143dupC	p.Ser49PhefsTer3	frameshift	Exon 2 of 11	ENSP00000323681.8	Q8NDL9-3
	AGBL5	ENST00000487078.5	TSL:1	n.143dupC		non_coding_transcript_exon	Exon 2 of 16	ENSP00000433830.1	Q8NDL9-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.1
Mutation Taster		=8/192	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1286076992; hg19: chr2-27275968;