NM_015633.3:c.184C>T

Variant names:

• chr12-26956591-C-T
• rs771881615
• NM_015633.3:c.184C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_015633.3(FGFR1OP2):​c.184C>T​(p.Arg62Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,600,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R62Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: FGFR1OP2 NM_015633.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.57
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.788

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGFR1OP2	NM_015633.3	MANE Select	c.184C>T	p.Arg62Trp	missense	Exon 3 of 7	NP_056448.1	Q9NVK5-1
	FGFR1OP2	NM_001171887.2		c.184C>T	p.Arg62Trp	missense	Exon 3 of 6	NP_001165358.1	Q9NVK5-2
	FGFR1OP2	NM_001171888.2		c.184C>T	p.Arg62Trp	missense	Exon 3 of 5	NP_001165359.1	Q9NVK5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGFR1OP2	ENST00000229395.8	TSL:2 MANE Select	c.184C>T	p.Arg62Trp	missense	Exon 3 of 7	ENSP00000229395.3	Q9NVK5-1
	FGFR1OP2	ENST00000546072.5	TSL:1	c.184C>T	p.Arg62Trp	missense	Exon 3 of 5	ENSP00000437556.1	Q9NVK5-3
	FGFR1OP2	ENST00000887799.1		c.184C>T	p.Arg62Trp	missense	Exon 4 of 8	ENSP00000557858.1

Frequencies

GnomAD3 genomes AF: 0.0000659 AC: 10 AN: 151706 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000592

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000203 AC: 5 AN: 246298 AF XY: 0.0000225

Gnomad AFR exome AF: 0.0000626

Gnomad AMR exome AF: 0.0000306

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000568

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000828 AC: 12 AN: 1448996 Hom.: 0 Cov.: 29 AF XY: 0.0000125 AC XY: 9 AN XY: 721212

African (AFR) AF: 0.0000302 AC: 1 AN: 33146

American (AMR) AF: 0.0000233 AC: 1 AN: 42848

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25822

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38784

South Asian (SAS) AF: 0.00 AC: 0 AN: 84888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52734

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5456

European-Non Finnish (NFE) AF: 0.00000633 AC: 7 AN: 1105708

Other (OTH) AF: 0.0000336 AC: 2 AN: 59610

GnomAD4 genome AF: 0.0000659 AC: 10 AN: 151706 Hom.: 0 Cov.: 31 AF XY: 0.0000675 AC XY: 5 AN XY: 74100

African (AFR) AF: 0.00 AC: 0 AN: 41312

American (AMR) AF: 0.000592 AC: 9 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67962

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000604

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.019	T
MetaRNN	Pathogenic	0.79	D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.6
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.90
MutPred		0.57		Gain of catalytic residue at M67 (P = 2e-04)
MVP		0.49
MPC		1.0
ClinPred		0.99	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.52
gMVP		0.64
Mutation Taster		=54/46	polymorphism

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: rs771881615; hg19: chr12-27109524;