12-2827276-TCC-CCT

Variant names:

• chr12-2827276-TCC-CCT
• NM_031474.3:c.775_777delGGAinsAGG
• NRIP2 p.Gly259Arg

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_031474.3(NRIP2):​c.775_777delGGAinsAGG​(p.Gly259Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G259E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NRIP2 NM_031474.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08
• Publications: 0 publications found

Genes affected

NRIP2 (HGNC:23078): (nuclear receptor interacting protein 2) Predicted to enable aspartic-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to act upstream of or within Notch signaling pathway and negative regulation of transcription by RNA polymerase II. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ITFG2 (HGNC:30879): (integrin alpha FG-GAP repeat containing 2) Involved in cellular response to amino acid starvation; cellular response to glucose starvation; and negative regulation of TORC1 signaling. Located in lysosomal membrane. Part of KICSTOR complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031474.3. 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
	NRIP2	NM_031474.3	MANE Select	c.775_777delGGAinsAGG	p.Gly259Arg	missense	N/A	NP_113662.1	Q9BQI9-1
	ITFG2	NR_130744.3		n.1573-2941_1573-2939delTCCinsCCT		intron	N/A
	ITFG2	NR_147202.2		n.1474+3024_1474+3026delTCCinsCCT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRIP2	ENST00000337508.9	TSL:1 MANE Select	c.775_777delGGAinsAGG	p.Gly259Arg	missense	N/A	ENSP00000337501.4	Q9BQI9-1
	ITFG2	ENST00000917240.1		c.*21-2941_*21-2939delTCCinsCCT		intron	N/A	ENSP00000587299.1
	ITFG2	ENST00000538822.1	TSL:5	n.*59+3024_*59+3026delTCCinsCCT		intron	N/A	ENSP00000442023.1	H0YG72

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-2936442;