chr2-100284417-T-C

Variant names:

• chr2-100284417-T-C
• rs1390505386
• NM_198461.4:c.2146A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198461.4(LONRF2):​c.2146A>G​(p.Ile716Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,454,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LONRF2 NM_198461.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.22
• Publications: 0 publications found

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

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14201692).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198461.4. 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
	LONRF2	NM_198461.4	MANE Select	c.2146A>G	p.Ile716Val	missense	Exon 12 of 12	NP_940863.3	Q1L5Z9-1
	LONRF2	NM_001371783.1		c.1417A>G	p.Ile473Val	missense	Exon 13 of 13	NP_001358712.1	Q1L5Z9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LONRF2	ENST00000393437.8	TSL:5 MANE Select	c.2146A>G	p.Ile716Val	missense	Exon 12 of 12	ENSP00000377086.3	Q1L5Z9-1
	LONRF2	ENST00000409647.1	TSL:2	c.1417A>G	p.Ile473Val	missense	Exon 12 of 12	ENSP00000386823.1	Q1L5Z9-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 236584 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1454800 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 2 AN XY: 722828

African (AFR) AF: 0.00 AC: 0 AN: 33380

American (AMR) AF: 0.00 AC: 0 AN: 43982

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25942

East Asian (EAS) AF: 0.00 AC: 0 AN: 39488

South Asian (SAS) AF: 0.00 AC: 0 AN: 84264

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52812

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1109096

Other (OTH) AF: 0.00 AC: 0 AN: 60076

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.65
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.60
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.74	N
PhyloP100		3.2
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	0.98	T
Polyphen		0.091	B
Vest4		0.22
MutPred		0.67		Gain of helix (P = 0.062)
MVP		0.32
MPC		0.36
ClinPred		0.27	T
GERP RS		1.1
Varity_R		0.027
gMVP		0.38
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs1390505386; hg19: chr2-100900879;