chr14-85621882-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013231.6(FLRT2):​c.368C>T​(p.Thr123Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,290 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

FLRT2
NM_013231.6 missense

Scores

4
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.90
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FLRT2NM_013231.6 linkuse as main transcriptc.368C>T p.Thr123Ile missense_variant 2/2 ENST00000330753.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FLRT2ENST00000330753.6 linkuse as main transcriptc.368C>T p.Thr123Ile missense_variant 2/21 NM_013231.6 P1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152172
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000808
AC:
2
AN:
247604
Hom.:
0
AF XY:
0.00000749
AC XY:
1
AN XY:
133598
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
37
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152290
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000165
AC:
2
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 submitterclinical testingAmbry GeneticsDec 14, 2023The c.368C>T (p.T123I) 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 368, causing the threonine (T) at amino acid position 123 to be replaced by an isoleucine (I). 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
Uncertain
0.55
BayesDel_addAF
Uncertain
0.079
D
BayesDel_noAF
Uncertain
0.10
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
T;T
Eigen
Pathogenic
0.74
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
.;D
M_CAP
Benign
0.023
T
MetaRNN
Uncertain
0.58
D;D
MetaSVM
Benign
-0.69
T
MutationAssessor
Benign
1.2
L;L
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.84
D
PROVEAN
Uncertain
-3.0
D;D
REVEL
Uncertain
0.36
Sift
Uncertain
0.017
D;D
Sift4G
Uncertain
0.0050
D;D
Polyphen
1.0
D;D
Vest4
0.71
MutPred
0.40
Loss of disorder (P = 0.1318);Loss of disorder (P = 0.1318);
MVP
0.64
MPC
0.68
ClinPred
0.58
D
GERP RS
5.7
Varity_R
0.30
gMVP
0.52

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.

Other links and lift over

dbSNP: rs554986569; hg19: chr14-86088226; API