14-85551578-A-G

Variant names:

• chr14-85551578-A-G
• rs985620
• NM_013231.6:c.-377+21044A>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+21044A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.948 in 152,282 control chromosomes in the GnomAD database, including 68,473 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 0.95 (68466 hom., cov: 32)
  • Exomes 𝑓: 1.0 (7 hom.)
• Consequence: FLRT2 NM_013231.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.752

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLRT2	NM_013231.6	c.-377+21044A>G		intron_variant	Intron 1 of 1	ENST00000330753.6	NP_037363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLRT2	ENST00000330753.6	c.-377+21044A>G		intron_variant	Intron 1 of 1	1	NM_013231.6	ENSP00000332879.4

Frequencies

GnomAD3 genomes AF: 0.948 AC: 144250 AN: 152150 Hom.: 68415 Cov.: 32

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.953

Gnomad AMR AF: 0.944

Gnomad ASJ AF: 0.985

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.938

Gnomad FIN AF: 0.969

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.948

GnomAD4 exome AF: 1.00 AC: 14 AN: 14 Hom.: 7 AF XY: 1.00 AC XY: 12 AN XY: 12

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.948 AC: 144361 AN: 152268 Hom.: 68466 Cov.: 32 AF XY: 0.948 AC XY: 70566 AN XY: 74442

Gnomad4 AFR AF: 0.954

Gnomad4 AMR AF: 0.944

Gnomad4 ASJ AF: 0.985

Gnomad4 EAS AF: 0.867

Gnomad4 SAS AF: 0.939

Gnomad4 FIN AF: 0.969

Gnomad4 NFE AF: 0.947

Gnomad4 OTH AF: 0.947

Alfa AF: 0.948 Hom.: 9711

Bravo AF: 0.947

Asia WGS AF: 0.903 AC: 3143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.1
DANN	Benign	0.86

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: rs985620; hg19: chr14-86017922;