Variant 12-26957706-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015633.3(FGFR1OP2):c.359C>T(p.Pro120Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,612,782 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

FGFR1OP2
NM_015633.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.73

Variant links:

Genes affected

FGFR1OP2 (HGNC:23098): (FGFR1 oncogene partner 2) Predicted to enable identical protein binding activity. Predicted to be involved in response to wounding. Predicted to act upstream of or within wound healing. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FGFR1OP2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FGFR1OP2	NM_015633.3 linkuse as main transcript	c.359C>T	p.Pro120Leu	missense_variant	4/7	ENST00000229395.8	NP_056448.1
FGFR1OP2	NM_001171887.2 linkuse as main transcript	c.359C>T	p.Pro120Leu	missense_variant	4/6		NP_001165358.1
FGFR1OP2	NM_001171888.2 linkuse as main transcript	c.359C>T	p.Pro120Leu	missense_variant	4/5		NP_001165359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGFR1OP2	ENST00000229395.8 linkuse as main transcript	c.359C>T	p.Pro120Leu	missense_variant	4/7	2	NM_015633.3	ENSP00000229395		Q9NVK5-1
FGFR1OP2	ENST00000546072.5 linkuse as main transcript	c.359C>T	p.Pro120Leu	missense_variant	4/5	1		ENSP00000437556		Q9NVK5-3
FGFR1OP2	ENST00000327214.5 linkuse as main transcript	c.359C>T	p.Pro120Leu	missense_variant	4/6	2		ENSP00000323763	P1	Q9NVK5-2
FGFR1OP2	ENST00000395941.4 linkuse as main transcript	n.600C>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151588

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251066

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461194

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726900

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151588

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73968

show subpopulations

Gnomad4 AFR

AF:

0.0000485

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

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 25, 2023

The c.359C>T (p.P120L) alteration is located in exon 4 (coding exon 3) of the FGFR1OP2 gene. This alteration results from a C to T substitution at nucleotide position 359, causing the proline (P) at amino acid position 120 to be replaced by a leucine (L). 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

0.14

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.21

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.054

T;.;.

Eigen

Benign

0.058

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.0056

MetaRNN

Uncertain

0.61

D;D;D

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.0

M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.22

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.27

T;T;T

Polyphen

0.062

B;B;B

Vest4

0.81

MVP

0.39

MPC

0.52

ClinPred

0.75

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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