12-26957711-A-G

Variant names:

• chr12-26957711-A-G
• rs745673091
• NM_015633.3:c.364A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015633.3(FGFR1OP2):​c.364A>G​(p.Ile122Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FGFR1OP2 NM_015633.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.81
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1517401).

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.364A>G	p.Ile122Val	missense	Exon 4 of 7	NP_056448.1	Q9NVK5-1
	FGFR1OP2	NM_001171887.2		c.364A>G	p.Ile122Val	missense	Exon 4 of 6	NP_001165358.1	Q9NVK5-2
	FGFR1OP2	NM_001171888.2		c.364A>G	p.Ile122Val	missense	Exon 4 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.364A>G	p.Ile122Val	missense	Exon 4 of 7	ENSP00000229395.3	Q9NVK5-1
	FGFR1OP2	ENST00000546072.5	TSL:1	c.364A>G	p.Ile122Val	missense	Exon 4 of 5	ENSP00000437556.1	Q9NVK5-3
	FGFR1OP2	ENST00000887799.1		c.364A>G	p.Ile122Val	missense	Exon 5 of 8	ENSP00000557858.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461450 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727026

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39620

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111794

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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	Benign	0.086
BayesDel_addAF	Benign	-0.0080	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.19
Eigen_PC	Benign	0.0065
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.8
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.069
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0090	B
Vest4		0.36
MutPred		0.42		Gain of catalytic residue at I122 (P = 0.0101)
MVP		0.39
MPC		0.29
ClinPred		0.47	T
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.088
gMVP		0.12
Mutation Taster		=75/25	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: rs745673091; hg19: chr12-27110644;