NM_013231.6:c.-377+22708A>G

Variant names:

• chr14-85553242-A-G
• rs1955418
• NM_013231.6:c.-377+22708A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLRT2	NM_013231.6	MANE Select	c.-377+22708A>G		intron	N/A	NP_037363.1
	FLRT2	NM_001346143.2		c.-377+19249A>G		intron	N/A	NP_001333072.1
	FLRT2	NM_001346144.2		c.-377+22686A>G		intron	N/A	NP_001333073.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLRT2	ENST00000330753.6	TSL:1 MANE Select	c.-377+22708A>G		intron	N/A	ENSP00000332879.4
	FLRT2	ENST00000554746.1	TSL:1	c.-377+22686A>G		intron	N/A	ENSP00000451050.1
	FLRT2	ENST00000682132.1		c.-377+19975A>G		intron	N/A	ENSP00000507088.1

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

African (AFR) AF: 0.624 AC: 25873 AN: 41456

American (AMR) AF: 0.905 AC: 13848 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.961 AC: 3336 AN: 3470

East Asian (EAS) AF: 0.779 AC: 4021 AN: 5164

South Asian (SAS) AF: 0.889 AC: 4292 AN: 4826

European-Finnish (FIN) AF: 0.969 AC: 10284 AN: 10614

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.945 AC: 64293 AN: 68032

Other (OTH) AF: 0.871 AC: 1841 AN: 2114

Alfa AF: 0.926 Hom.: 74570

Bravo AF: 0.832

Asia WGS AF: 0.828 AC: 2881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.7
DANN	Benign	0.62
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

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: rs1955418; hg19: chr14-86019586;