Variant chr14-85622734-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013231.6(FLRT2):c.1220C>T(p.Thr407Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

FLRT2
NM_013231.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.87

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08294693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLRT2	NM_013231.6 linkuse as main transcript	c.1220C>T	p.Thr407Met	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.1220C>T	p.Thr407Met	missense_variant	2/2	1	NM_013231.6	P1
FLRT2	ENST00000554746.1 linkuse as main transcript	c.1220C>T	p.Thr407Met	missense_variant	2/2	1		P1
FLRT2	ENST00000682132.1 linkuse as main transcript	c.1220C>T	p.Thr407Met	missense_variant	2/2			P1
FLRT2	ENST00000683129.1 linkuse as main transcript	c.1220C>T	p.Thr407Met	missense_variant	2/2			P1

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000716

AC:

AN:

251280

Hom.:

AF XY:

0.0000957

AC XY:

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000360

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000376

AC:

AN:

1461786

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000475

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000216

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.1220C>T (p.T407M) alteration is located in exon 2 (coding exon 1) of the FLRT2 gene. This alteration results from a C to T substitution at nucleotide position 1220, causing the threonine (T) at amino acid position 407 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.050

T;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.78

.;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.083

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.20

N;N

MutationTaster

Benign

0.98

D;D

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.22

N;N

REVEL

Benign

0.14

Sift

Benign

0.10

T;T

Sift4G

Benign

0.11

T;T

Polyphen

1.0

D;D

Vest4

0.37

MVP

0.47

MPC

0.45

ClinPred

0.058

GERP RS

5.3

Varity_R

0.040

gMVP

0.35

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