rs1955412

chr14-85546450-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013231.6(FLRT2):c.-377+15916T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 151,952 control chromosomes in the GnomAD database, including 4,315 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4315 hom., cov: 32)
• Consequence: FLRT2 NM_013231.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLRT2	NM_013231.6	c.-377+15916T>C		intron_variant		ENST00000330753.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLRT2	ENST00000330753.6	c.-377+15916T>C		intron_variant		1	NM_013231.6	P1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35489 AN: 151834 Hom.: 4311 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.194

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.234 AC: 35496 AN: 151952 Hom.: 4315 Cov.: 32 AF XY: 0.235 AC XY: 17449 AN XY: 74272

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.192

Alfa AF: 0.248 Hom.: 2257

Bravo AF: 0.219

Asia WGS AF: 0.199 AC: 696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.6
Dann	Benign	0.58

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

Other links and lift over

dbSNP: rs1955412; hg19: chr14-86012794;