Genetic Variant FGFR1OP2:p.Ala57Thr (chr12-26956576-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015633.3(FGFR1OP2):c.169G>A(p.Ala57Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,589,640 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

FGFR1OP2
NM_015633.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.41

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015633.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FGFR1OP2	NM_015633.3	MANE Select	c.169G>A	p.Ala57Thr	missense	Exon 3 of 7	NP_056448.1	Q9NVK5-1
FGFR1OP2	NM_001171887.2		c.169G>A	p.Ala57Thr	missense	Exon 3 of 6	NP_001165358.1	Q9NVK5-2
FGFR1OP2	NM_001171888.2		c.169G>A	p.Ala57Thr	missense	Exon 3 of 5	NP_001165359.1	Q9NVK5-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FGFR1OP2	ENST00000229395.8	TSL:2 MANE Select	c.169G>A	p.Ala57Thr	missense	Exon 3 of 7	ENSP00000229395.3	Q9NVK5-1
FGFR1OP2	ENST00000546072.5	TSL:1	c.169G>A	p.Ala57Thr	missense	Exon 3 of 5	ENSP00000437556.1	Q9NVK5-3
FGFR1OP2	ENST00000887799.1		c.169G>A	p.Ala57Thr	missense	Exon 4 of 8	ENSP00000557858.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000820

AC:

AN:

243798

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000316

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.00000973

AC:

AN:

1438532

Hom.:

Cov.:

AF XY:

0.00000698

AC XY:

AN XY:

716144

show subpopulations

African (AFR)

AF:

0.0000304

AC:

AN:

32896

American (AMR)

AF:

0.0000478

AC:

AN:

41828

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25566

East Asian (EAS)

AF:

0.00

AC:

AN:

38208

South Asian (SAS)

AF:

0.0000119

AC:

AN:

83706

European-Finnish (FIN)

AF:

0.0000192

AC:

AN:

52048

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5320

European-Non Finnish (NFE)

AF:

0.00000727

AC:

AN:

1099962

Other (OTH)

AF:

0.0000169

AC:

AN:

58998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151108

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73712

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41150

American (AMR)

AF:

0.00

AC:

AN:

15130

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10196

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67892

Other (OTH)

AF:

0.00

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000354

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Pathogenic

0.23

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

M_CAP

Benign

0.0069

MetaRNN

Uncertain

0.60

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.6

PhyloP100

7.4

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-2.0

REVEL

Uncertain

0.30

Sift

Benign

0.087

Sift4G

Uncertain

0.014

Polyphen

0.95

Vest4

0.64

MVP

0.50

MPC

0.43

ClinPred

0.83

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.24

gMVP

0.52

Mutation Taster

=65/35

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over