NM_013231.6:c.809C>A

Variant names:

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

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>A​(p.Thr270Lys) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T270I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FLRT2 NM_013231.6 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.17608362).

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>A	p.Thr270Lys	missense	Exon 2 of 2	NP_037363.1	O43155
	FLRT2	NM_001346143.2		c.809C>A	p.Thr270Lys	missense	Exon 2 of 2	NP_001333072.1	O43155
	FLRT2	NM_001346144.2		c.809C>A	p.Thr270Lys	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>A	p.Thr270Lys	missense	Exon 2 of 2	ENSP00000332879.4	O43155
	FLRT2	ENST00000554746.1	TSL:1	c.809C>A	p.Thr270Lys	missense	Exon 2 of 2	ENSP00000451050.1	O43155
	FLRT2	ENST00000682132.1		c.809C>A	p.Thr270Lys	missense	Exon 2 of 2	ENSP00000507088.1	O43155

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.064	T
Eigen	Benign	-0.075
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.23	N
PhyloP100		3.2
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.15
Sift	Benign	0.11	T
Sift4G	Benign	0.55	T
Polyphen		0.095	B
Vest4		0.42
MutPred		0.43		Gain of ubiquitination at T270 (P = 0.0258)
MVP		0.46
MPC		0.36
ClinPred		0.26	T
GERP RS		6.0
Varity_R		0.15
gMVP		0.50
Mutation Taster		=69/31	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;