rs11123823

Positions:

• chr2-100299853-A-C
• chr2-100299853-A-G
• chr2-100299853-A-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_198461.4(LONRF2):​c.1131T>G​(p.Gly377Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: LONRF2 NM_198461.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.818

Genes affected

LONRF2 (HGNC:24788): (LON peptidase N-terminal domain and ring finger 2) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=0.818 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LONRF2	NM_198461.4	c.1131T>G	p.Gly377Gly	synonymous_variant	5/12	ENST00000393437.8	NP_940863.3
LONRF2	NM_001371783.1	c.402T>G	p.Gly134Gly	synonymous_variant	6/13		NP_001358712.1
LONRF2	XM_047443537.1	c.402T>G	p.Gly134Gly	synonymous_variant	5/12		XP_047299493.1
LONRF2	XM_047443538.1	c.1131T>G	p.Gly377Gly	synonymous_variant	5/6		XP_047299494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LONRF2	ENST00000393437.8	c.1131T>G	p.Gly377Gly	synonymous_variant	5/12	5	NM_198461.4	ENSP00000377086.3
LONRF2	ENST00000409647.1	c.402T>G	p.Gly134Gly	synonymous_variant	5/12	2		ENSP00000386823.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.6
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs11123823; hg19: chr2-100916315;