Variant 17-28880824-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004475.3(FLOT2):c.1137T>G(p.Asp379Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0043 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FLOT2
NM_004475.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.708

Variant links:

Genes affected

FLOT2 (HGNC:3758): (flotillin 2) Caveolae are small domains on the inner cell membrane involved in vesicular trafficking and signal transduction. This gene encodes a caveolae-associated, integral membrane protein, which is thought to function in neuronal signaling. [provided by RefSeq, Jul 2008]

FLOT2 links:

FLOT2 (HGNC:):

FLOT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.099199116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLOT2	NM_004475.3 linkuse as main transcript	c.1137T>G	p.Asp379Glu	missense_variant	10/11	ENST00000394908.9	NP_004466.2	Q14254A0A024QZ62Q9BTI6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLOT2	ENST00000394908.9 linkuse as main transcript	c.1137T>G	p.Asp379Glu	missense_variant	10/11	1	NM_004475.3	ENSP00000378368.3		Q14254

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151932

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00431

AC:

6062

AN:

1407952

Hom.:

Cov.:

AF XY:

0.00394

AC XY:

2766

AN XY:

702498

show subpopulations

Gnomad4 AFR exome

AF:

0.00366

Gnomad4 AMR exome

AF:

0.000247

Gnomad4 ASJ exome

AF:

0.00128

Gnomad4 EAS exome

AF:

0.000972

Gnomad4 SAS exome

AF:

0.00149

Gnomad4 FIN exome

AF:

0.000416

Gnomad4 NFE exome

AF:

0.00519

Gnomad4 OTH exome

AF:

0.00306

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000263

AC:

AN:

152050

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000190

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2022

The c.1137T>G (p.D379E) alteration is located in exon 10 (coding exon 10) of the FLOT2 gene. This alteration results from a T to G substitution at nucleotide position 1137, causing the aspartic acid (D) at amino acid position 379 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.079

T;T;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.34

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.0058

MetaRNN

Benign

0.099

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

.;L;.

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.22

N;N;.

REVEL

Benign

0.13

Sift

Benign

0.52

T;T;.

Sift4G

Benign

0.41

T;T;T

Polyphen

0.0010

.;B;.

Vest4

0.23

MutPred

0.32

.;Loss of ubiquitination at K377 (P = 0.1343);Loss of ubiquitination at K377 (P = 0.1343);

MVP

0.16

MPC

0.52

ClinPred

0.23

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.069

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over