14-85553242-A-G

Position:

• chr14-85553242-A-G

Variant summary

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

The NM_013231.6(FLRT2):​c.-377+22708A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 152,178 control chromosomes in the GnomAD database, including 56,116 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 0.85 (56116 hom., cov: 32)
• Consequence: FLRT2 NM_013231.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.298

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLRT2	NM_013231.6	c.-377+22708A>G		intron_variant		ENST00000330753.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLRT2	ENST00000330753.6	c.-377+22708A>G		intron_variant		1	NM_013231.6	P1

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128869 AN: 152062 Hom.: 56097 Cov.: 32

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.953

Gnomad AMR AF: 0.905

Gnomad ASJ AF: 0.961

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.969

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.871

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

GnomAD4 genome AF: 0.847 AC: 128930 AN: 152178 Hom.: 56116 Cov.: 32 AF XY: 0.850 AC XY: 63256 AN XY: 74406

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.905

Gnomad4 ASJ AF: 0.961

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.889

Gnomad4 FIN AF: 0.969

Gnomad4 NFE AF: 0.945

Gnomad4 OTH AF: 0.871

Alfa AF: 0.930 Hom.: 62209

Bravo AF: 0.832

Asia WGS AF: 0.828 AC: 2881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.7
DANN	Benign	0.62

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: rs1955418; hg19: chr14-86019586;