14-85622323-C-T

Variant names:

• chr14-85622323-C-T
• rs1049827519
• NM_013231.6:c.809C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013231.6(FLRT2):​c.809C>T​(p.Thr270Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FLRT2 NM_013231.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.24
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22481495).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013231.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLRT2	NM_013231.6	MANE Select	c.809C>T	p.Thr270Ile	missense	Exon 2 of 2	NP_037363.1	O43155
	FLRT2	NM_001346143.2		c.809C>T	p.Thr270Ile	missense	Exon 2 of 2	NP_001333072.1	O43155
	FLRT2	NM_001346144.2		c.809C>T	p.Thr270Ile	missense	Exon 2 of 2	NP_001333073.1	O43155

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLRT2	ENST00000330753.6	TSL:1 MANE Select	c.809C>T	p.Thr270Ile	missense	Exon 2 of 2	ENSP00000332879.4	O43155
	FLRT2	ENST00000554746.1	TSL:1	c.809C>T	p.Thr270Ile	missense	Exon 2 of 2	ENSP00000451050.1	O43155
	FLRT2	ENST00000682132.1		c.809C>T	p.Thr270Ile	missense	Exon 2 of 2	ENSP00000507088.1	O43155

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.2
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.15
Sift	Uncertain	0.014	D
Sift4G	Benign	0.097	T
Polyphen		0.17	B
Vest4		0.35
MutPred		0.33		Loss of helix (P = 0.2022)
MVP		0.32
MPC		0.46
ClinPred		0.74	D
GERP RS		6.0
Varity_R		0.15
gMVP		0.36
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs1049827519; hg19: chr14-86088667;