14-85551578-A-G

Variant names:

• chr14-85551578-A-G
• rs985620
• NM_013231.6:c.-377+21044A>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+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
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.946 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+21044A>G		intron	N/A	NP_037363.1
	FLRT2	NM_001346143.2		c.-377+17585A>G		intron	N/A	NP_001333072.1
	FLRT2	NM_001346144.2		c.-377+21022A>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+21044A>G		intron	N/A	ENSP00000332879.4
	FLRT2	ENST00000554746.1	TSL:1	c.-377+21022A>G		intron	N/A	ENSP00000451050.1
	FLRT2	ENST00000682132.1		c.-377+18311A>G		intron	N/A	ENSP00000507088.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 1.00 AC: 8 AN: 8

Other (OTH) AF: 1.00 AC: 4 AN: 4

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

African (AFR) AF: 0.954 AC: 39620 AN: 41550

American (AMR) AF: 0.944 AC: 14438 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.985 AC: 3419 AN: 3472

East Asian (EAS) AF: 0.867 AC: 4486 AN: 5172

South Asian (SAS) AF: 0.939 AC: 4530 AN: 4826

European-Finnish (FIN) AF: 0.969 AC: 10288 AN: 10618

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.947 AC: 64428 AN: 68022

Other (OTH) AF: 0.947 AC: 1998 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.1
DANN	Benign	0.86
PhyloP100		-0.75
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: rs985620; hg19: chr14-86017922;