17-28882027-G-C

Position:

• chr17-28882027-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004475.3(FLOT2):​c.701C>G​(p.Thr234Arg) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FLOT2 NM_004475.3 missense, splice_region
• Scores: Splicing: ADA: 0.01090
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.05

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23904541).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLOT2	NM_004475.3	c.701C>G	p.Thr234Arg	missense_variant, splice_region_variant	8/11	ENST00000394908.9	NP_004466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLOT2	ENST00000394908.9	c.701C>G	p.Thr234Arg	missense_variant, splice_region_variant	8/11	1	NM_004475.3	ENSP00000378368.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 24, 2023

The c.701C>G (p.T234R) alteration is located in exon 8 (coding exon 8) of the FLOT2 gene. This alteration results from a C to G substitution at nucleotide position 701, causing the threonine (T) at amino acid position 234 to be replaced by an arginine (R). 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	0.087
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.084	T;T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.11
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.35	.;N;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	2.6	N;N;.
REVEL	Benign	0.18
Sift	Benign	0.28	T;T;.
Sift4G	Benign	0.33	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.47
MutPred		0.32		.;Loss of glycosylation at T234 (P = 0.0216);Loss of glycosylation at T234 (P = 0.0216);
MVP		0.53
MPC		0.63
ClinPred		0.83	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.91

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.011
dbscSNV1_RF	Benign	0.12
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-27209045;