Variant 2-100298868-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_198461.4(LONRF2):c.1444C>A(p.His482Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00919 in 1,614,110 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0070 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0094 ( 79 hom. )

Consequence

LONRF2
NM_198461.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.12

Variant links:

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]

LONRF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00684464).

BP6

Variant 2-100298868-G-T is Benign according to our data. Variant chr2-100298868-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2651206.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LONRF2	NM_198461.4 link	c.1444C>A	p.His482Asn	missense_variant	7/12	ENST00000393437.8	NP_940863.3	Q1L5Z9-1
LONRF2	NM_001371783.1 link	c.715C>A	p.His239Asn	missense_variant	8/13		NP_001358712.1
LONRF2	XM_047443537.1 link	c.715C>A	p.His239Asn	missense_variant	7/12		XP_047299493.1
LONRF2	XM_047443538.1 link	c.*33C>A		3_prime_UTR_variant	6/6		XP_047299494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LONRF2	ENST00000393437.8 link	c.1444C>A	p.His482Asn	missense_variant	7/12	5	NM_198461.4	ENSP00000377086.3		Q1L5Z9-1
LONRF2	ENST00000409647.1 link	c.715C>A	p.His239Asn	missense_variant	7/12	2		ENSP00000386823.1		Q1L5Z9-2

Frequencies

GnomAD3 genomes

AF:

0.00702

AC:

1069

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00425

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0210

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00977

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.00730

AC:

1836

AN:

251478

Hom.:

AF XY:

0.00731

AC XY:

993

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00399

Gnomad ASJ exome

AF:

0.00427

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000751

Gnomad FIN exome

AF:

0.0199

Gnomad NFE exome

AF:

0.00991

Gnomad OTH exome

AF:

0.00749

GnomAD4 exome

AF:

0.00942

AC:

13771

AN:

1461794

Hom.:

Cov.:

AF XY:

0.00914

AC XY:

6645

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00125

Gnomad4 AMR exome

AF:

0.00385

Gnomad4 ASJ exome

AF:

0.00536

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000974

Gnomad4 FIN exome

AF:

0.0193

Gnomad4 NFE exome

AF:

0.0107

Gnomad4 OTH exome

AF:

0.00672

GnomAD4 genome

AF:

0.00702

AC:

1069

AN:

152316

Hom.:

Cov.:

AF XY:

0.00716

AC XY:

533

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00190

Gnomad4 AMR

AF:

0.00425

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0210

Gnomad4 NFE

AF:

0.00976

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.00872

Hom.:

Bravo

AF:

0.00585

TwinsUK

AF:

0.0127

AC:

ALSPAC

AF:

0.00934

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0101

AC:

ExAC

AF:

0.00742

AC:

901

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00916

EpiControl

AF:

0.00936

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

LONRF2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

CADD

Benign

9.4

DANN

Benign

0.75

DEOGEN2

Benign

0.023

T;.

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.65

T;T

MetaRNN

Benign

0.0068

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.42

N;.

PrimateAI

Benign

0.48

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.049

Sift

Benign

0.17

T;T

Sift4G

Benign

0.52

T;T

Polyphen

0.0030

B;.

Vest4

0.21

MVP

0.30

MPC

0.39

ClinPred

0.016

GERP RS

2.1

Varity_R

0.080

gMVP

0.33

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over