rs746030640

Variant names:

• chr2-100284335-C-A
• rs746030640
• NM_198461.4:c.2228G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-100284335-C-A
• chr2-100284335-C-T

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.2228G>T​(p.Arg743Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R743Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: LONRF2 NM_198461.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.806
• 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=0.18206385).

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.2228G>T	p.Arg743Leu	missense	Exon 12 of 12	NP_940863.3	Q1L5Z9-1
	LONRF2	NM_001371783.1		c.1499G>T	p.Arg500Leu	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.2228G>T	p.Arg743Leu	missense	Exon 12 of 12	ENSP00000377086.3	Q1L5Z9-1
	LONRF2	ENST00000409647.1	TSL:2	c.1499G>T	p.Arg500Leu	missense	Exon 12 of 12	ENSP00000386823.1	Q1L5Z9-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1424640 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 704330

African (AFR) AF: 0.00 AC: 0 AN: 32852

American (AMR) AF: 0.00 AC: 0 AN: 39782

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25348

East Asian (EAS) AF: 0.00 AC: 0 AN: 38568

South Asian (SAS) AF: 0.0000124 AC: 1 AN: 80776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1091324

Other (OTH) AF: 0.00 AC: 0 AN: 58770

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.66	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.81
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.54
Sift	Uncertain	0.022	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.17	B
Vest4		0.29
MutPred		0.49		Loss of MoRF binding (P = 0.0111)
MVP		0.85
MPC		0.56
ClinPred		0.36	T
GERP RS		3.4
Varity_R		0.086
gMVP		0.75
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs746030640; hg19: chr2-100900797;