12-26963366-A-G

Position:

• chr12-26963366-A-G

Variant summary

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

The NM_015633.3(FGFR1OP2):​c.535A>G​(p.Ile179Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FGFR1OP2 NM_015633.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.48

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

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	UniProt
FGFR1OP2	NM_015633.3	c.535A>G	p.Ile179Val	missense_variant	6/7	ENST00000229395.8	NP_056448.1
FGFR1OP2	NM_001171887.2	c.421A>G	p.Ile141Val	missense_variant	5/6		NP_001165358.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGFR1OP2	ENST00000229395.8	c.535A>G	p.Ile179Val	missense_variant	6/7	2	NM_015633.3	ENSP00000229395
FGFR1OP2	ENST00000327214.5	c.421A>G	p.Ile141Val	missense_variant	5/6	2		ENSP00000323763	P1
FGFR1OP2	ENST00000538172.1	n.2371A>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Oct 04, 2022

The c.535A>G (p.I179V) alteration is located in exon 6 (coding exon 5) of the FGFR1OP2 gene. This alteration results from a A to G substitution at nucleotide position 535, causing the isoleucine (I) at amino acid position 179 to be replaced by a valine (V). 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	0.30
BayesDel_addAF	Benign	0.0078	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.0027	T
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.2	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.66	N;N
REVEL	Uncertain	0.34
Sift	Benign	0.16	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.58	P;B
Vest4		0.65
MutPred		0.62		Gain of disorder (P = 0.143);.;
MVP		0.50
MPC		0.30
ClinPred		0.78	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs1939131460; hg19: chr12-27116299; COSMIC: COSV99986895; COSMIC: COSV99986895;