Variant chr14-85622688-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_013231.6(FLRT2):c.1174A>G(p.Ser392Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,613,936 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 8 hom. )

Consequence

FLRT2
NM_013231.6 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.13

Variant links:

Genes affected

FLRT2 (HGNC:3761): (fibronectin leucine rich transmembrane protein 2) This gene encodes a member of the fibronectin leucine rich transmembrane (FLRT) family of cell adhesion molecules, which regulate early embryonic vascular and neural development. The encoded type I transmembrane protein has an extracellular region consisting of an N-terminal leucine-rich repeat domain and a type 3 fibronectin domain, followed by a transmembrane domain and a short C-terminal cytoplasmic tail domain. It functions as both a homophilic cell adhesion molecule and a heterophilic chemorepellent through its interaction with members of the uncoordinated-5 receptor family. Proteolytic removal of the extracellular region controls the migration of neurons in the developing cortex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

FLRT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003712356).

BP6

Variant 14-85622688-A-G is Benign according to our data. Variant chr14-85622688-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 711387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLRT2	NM_013231.6 linkuse as main transcript	c.1174A>G	p.Ser392Gly	missense_variant	2/2	ENST00000330753.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FLRT2	ENST00000330753.6 linkuse as main transcript	c.1174A>G	p.Ser392Gly	missense_variant	2/2	1	NM_013231.6	P1
FLRT2	ENST00000554746.1 linkuse as main transcript	c.1174A>G	p.Ser392Gly	missense_variant	2/2	1		P1
FLRT2	ENST00000682132.1 linkuse as main transcript	c.1174A>G	p.Ser392Gly	missense_variant	2/2			P1
FLRT2	ENST00000683129.1 linkuse as main transcript	c.1174A>G	p.Ser392Gly	missense_variant	2/2			P1

Frequencies

GnomAD3 genomes

AF:

0.00135

AC:

205

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00510

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00212

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00142

AC:

356

AN:

251386

Hom.:

AF XY:

0.00149

AC XY:

202

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00565

Gnomad NFE exome

AF:

0.00193

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00107

AC:

1566

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

809

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00517

Gnomad4 NFE exome

AF:

0.00110

Gnomad4 OTH exome

AF:

0.000795

GnomAD4 genome

AF:

0.00135

AC:

205

AN:

152108

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00510

Gnomad4 NFE

AF:

0.00212

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00140

Hom.:

Bravo

AF:

0.000793

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.00156

AC:

189

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.57

CADD

Benign

5.9

DANN

Benign

0.19

DEOGEN2

Benign

0.059

T;T

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.71

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.47

.;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.0037

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.90

N;N

MutationTaster

Benign

0.89

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.52

N;N

REVEL

Benign

0.068

Sift

Benign

0.63

T;T

Sift4G

Benign

0.43

T;T

Polyphen

0.0

B;B

Vest4

0.053

MVP

0.42

MPC

0.27

ClinPred

0.017

GERP RS

2.6

Varity_R

0.021

gMVP

0.23

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