chr3-50348148-TG-T

Variant names:

• chr3-50348148-TG-T
• NM_006545.5:c.907delC

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_006545.5(NPRL2):​c.907delC​(p.Gln303SerfsTer11) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NPRL2 NM_006545.5 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 8.07

Genes affected

NPRL2 (HGNC:24969): (NPR2 like, GATOR1 complex subunit) Enables protein kinase activity. Contributes to GTPase activator activity. Involved in cellular response to amino acid starvation; negative regulation of TOR signaling; and negative regulation of kinase activity. Located in lysosomal membrane. Part of GATOR1 complex. Implicated in focal epilepsy. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Pathogenic. Variant got 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 3-50348148-TG-T is Pathogenic according to our data. Variant chr3-50348148-TG-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2445421.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPRL2	NM_006545.5	c.907delC	p.Gln303SerfsTer11	frameshift_variant	Exon 9 of 11	ENST00000232501.8	NP_006536.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPRL2	ENST00000232501.8	c.907delC	p.Gln303SerfsTer11	frameshift_variant	Exon 9 of 11	1	NM_006545.5	ENSP00000232501.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial focal epilepsy with variable foci Pathogenic:1

-

Pediatrics, Sichuan Provincial Hospital For Women And Children

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

The patient was a 2-month old female with recurrent seizures，Global development delay.Her brother, a carrier of the same gene mutation, was diagnosed with autism. -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: chr3-50385579;