20-64084214-CGG-TCT

Variant names:

• chr20-64084214-CGG-TCT
• NM_001353425.2:c.4_6delCCGinsAGA
• LKAAEAR1 p.Pro2Arg

Variant summary

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

The NM_001353425.2(LKAAEAR1):​c.4_6delCCGinsAGA​(p.Pro2Arg) 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LKAAEAR1 NM_001353425.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19
• Publications: 0 publications found

Genes affected

LKAAEAR1 (HGNC:33718): (LKAAEAR motif containing 1)

OPRL1 (HGNC:8155): (opioid related nociceptin receptor 1) The protein encoded by this gene is a member of the 7 transmembrane-spanning G protein-coupled receptor family, and functions as a receptor for the endogenous, opioid-related neuropeptide, nociceptin/orphanin FQ. This receptor-ligand system modulates a variety of biological functions and neurobehavior, including stress responses and anxiety behavior, learning and memory, locomotor activity, and inflammatory and immune responses. A promoter region between this gene and the 5'-adjacent RGS19 (regulator of G-protein signaling 19) gene on the opposite strand functions bi-directionally as a core-promoter for both genes, suggesting co-operative transcriptional regulation of these two functionally related genes. Alternatively spliced transcript variants have been described for this gene. A recent study provided evidence for translational readthrough in this gene, and expression of an additional C-terminally extended isoform via the use of an alternative in-frame translation termination codon. [provided by RefSeq, Dec 2017]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353425.2. 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
	LKAAEAR1	NM_001353425.2	MANE Select	c.4_6delCCGinsAGA	p.Pro2Arg	missense	N/A	NP_001340354.1	Q8TD35-1
	OPRL1	NM_182647.4	MANE Select	c.-185+3862_-185+3864delCGGinsTCT		intron	N/A	NP_872588.1	P41146-1
	LKAAEAR1	NM_001007125.3		c.4_6delCCGinsAGA	p.Pro2Arg	missense	N/A	NP_001007126.1	Q8TD35-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LKAAEAR1	ENST00000302096.5	TSL:2 MANE Select	c.4_6delCCGinsAGA	p.Pro2Arg	missense	N/A	ENSP00000302763.4	Q8TD35-1
	LKAAEAR1	ENST00000308906.6	TSL:1	c.4_6delCCGinsAGA	p.Pro2Arg	missense	N/A	ENSP00000310801.2	Q8TD35-2
	OPRL1	ENST00000336866.7	TSL:5 MANE Select	c.-185+3862_-185+3864delCGGinsTCT		intron	N/A	ENSP00000336843.2	P41146-1

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		2.2

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: chr20-62715567;