2-100295518-C-T

Variant names:

• chr2-100295518-C-T
• rs116227203
• NM_198461.4:c.1512G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_198461.4(LONRF2):​c.1512G>A​(p.Leu504Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,613,462 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (55 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (37 hom.)
• Consequence: LONRF2 NM_198461.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.806
• Publications: 2 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 2-100295518-C-T is Benign according to our data. Variant chr2-100295518-C-T is described in ClinVar as Benign. ClinVar VariationId is 711331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.806 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0128 (1950/152208) while in subpopulation AFR AF = 0.0447 (1857/41508). AF 95% confidence interval is 0.043. There are 55 homozygotes in GnomAd4. There are 908 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 55 gene

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.1512G>A	p.Leu504Leu	synonymous	Exon 8 of 12	NP_940863.3	Q1L5Z9-1
	LONRF2	NM_001371783.1		c.783G>A	p.Leu261Leu	synonymous	Exon 9 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.1512G>A	p.Leu504Leu	synonymous	Exon 8 of 12	ENSP00000377086.3	Q1L5Z9-1
	LONRF2	ENST00000409647.1	TSL:2	c.783G>A	p.Leu261Leu	synonymous	Exon 8 of 12	ENSP00000386823.1	Q1L5Z9-2

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1945 AN: 152090 Hom.: 54 Cov.: 33

Gnomad AFR AF: 0.0447

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00439

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.0101

GnomAD2 exomes AF: 0.00338 AC: 848 AN: 250994 AF XY: 0.00254

Gnomad AFR exome AF: 0.0469

Gnomad AMR exome AF: 0.00198

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00139 AC: 2030 AN: 1461254 Hom.: 37 Cov.: 30 AF XY: 0.00119 AC XY: 862 AN XY: 726948

African (AFR) AF: 0.0505 AC: 1689 AN: 33448

American (AMR) AF: 0.00257 AC: 115 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53286

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5766

European-Non Finnish (NFE) AF: 0.0000297 AC: 33 AN: 1111766

Other (OTH) AF: 0.00287 AC: 173 AN: 60376

GnomAD4 genome AF: 0.0128 AC: 1950 AN: 152208 Hom.: 55 Cov.: 33 AF XY: 0.0122 AC XY: 908 AN XY: 74422

African (AFR) AF: 0.0447 AC: 1857 AN: 41508

American (AMR) AF: 0.00438 AC: 67 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68022

Other (OTH) AF: 0.00995 AC: 21 AN: 2110

Alfa AF: 0.00595 Hom.: 7

Bravo AF: 0.0145

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	6.5
DANN	Benign	0.73
PhyloP100		0.81
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs116227203; hg19: chr2-100911980;