Variant 6-40392526-G-A 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_020737.3(LRFN2):c.1787C>T(p.Pro596Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,588,518 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 24 hom. )

Consequence

LRFN2
NM_020737.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.647

Variant links:

Genes affected

LRFN2 (HGNC:21226): (leucine rich repeat and fibronectin type III domain containing 2) Predicted to be involved in modulation of chemical synaptic transmission and regulation of postsynapse organization. Predicted to be located in plasma membrane. Predicted to be active in Schaffer collateral - CA1 synapse and cell surface. Predicted to be integral component of postsynaptic density membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRFN2 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=0.00382787).

BP6

Variant 6-40392526-G-A is Benign according to our data. Variant chr6-40392526-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2656538.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 526 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRFN2	NM_020737.3 linkuse as main transcript	c.1787C>T	p.Pro596Leu	missense_variant	3/3	ENST00000338305.7	NP_065788.1	Q9ULH4
LRFN2	XM_011514762.3 linkuse as main transcript	c.1787C>T	p.Pro596Leu	missense_variant	3/3		XP_011513064.1	Q9ULH4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRFN2	ENST00000338305.7 linkuse as main transcript	c.1787C>T	p.Pro596Leu	missense_variant	3/3	1	NM_020737.3	ENSP00000345985.6		Q9ULH4
LRFN2	ENST00000700335.1 linkuse as main transcript	c.1787C>T	p.Pro596Leu	missense_variant	4/4			ENSP00000514953.1		A0A8V8TQ63

Frequencies

GnomAD3 genomes

AF:

0.00346

AC:

526

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0187

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00363

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00430

AC:

872

AN:

202814

Hom.:

AF XY:

0.00453

AC XY:

511

AN XY:

112700

show subpopulations

Gnomad AFR exome

AF:

0.000261

Gnomad AMR exome

AF:

0.00128

Gnomad ASJ exome

AF:

0.00635

Gnomad EAS exome

AF:

0.000132

Gnomad SAS exome

AF:

0.00401

Gnomad FIN exome

AF:

0.0190

Gnomad NFE exome

AF:

0.00404

Gnomad OTH exome

AF:

0.00382

GnomAD4 exome

AF:

0.00331

AC:

4749

AN:

1436176

Hom.:

Cov.:

AF XY:

0.00340

AC XY:

2426

AN XY:

713618

show subpopulations

Gnomad4 AFR exome

AF:

0.000426

Gnomad4 AMR exome

AF:

0.00121

Gnomad4 ASJ exome

AF:

0.00508

Gnomad4 EAS exome

AF:

0.000105

Gnomad4 SAS exome

AF:

0.00517

Gnomad4 FIN exome

AF:

0.0187

Gnomad4 NFE exome

AF:

0.00277

Gnomad4 OTH exome

AF:

0.00316

GnomAD4 genome

AF:

0.00345

AC:

526

AN:

152342

Hom.:

Cov.:

AF XY:

0.00400

AC XY:

298

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.0187

Gnomad4 NFE

AF:

0.00363

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00327

Hom.:

Bravo

AF:

0.00196

ESP6500AA

AF:

0.000255

AC:

ESP6500EA

AF:

0.00329

AC:

ExAC

AF:

0.00404

AC:

474

Asia WGS

AF:

0.00491

AC:

AN:

3478

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

Sep 01, 2022

LRFN2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.84

DANN

Benign

0.89

DEOGEN2

Uncertain

0.47

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.2

REVEL

Benign

0.064

Sift

Benign

0.20

Sift4G

Benign

0.085

Polyphen

0.0

Vest4

0.049

MVP

0.38

MPC

0.39

ClinPred

0.0018

GERP RS

-1.3

Varity_R

0.031

gMVP

0.19

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