12-26957706-C-T

Variant names:

• chr12-26957706-C-T
• rs369150262
• NM_015633.3:c.359C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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 (★). Synonymous variant affecting the same amino acid position (i.e. P120P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: FGFR1OP2 NM_015633.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.73
• 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 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGFR1OP2	NM_015633.3	MANE Select	c.359C>T	p.Pro120Leu	missense	Exon 4 of 7	NP_056448.1	Q9NVK5-1
	FGFR1OP2	NM_001171887.2		c.359C>T	p.Pro120Leu	missense	Exon 4 of 6	NP_001165358.1	Q9NVK5-2
	FGFR1OP2	NM_001171888.2		c.359C>T	p.Pro120Leu	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.359C>T	p.Pro120Leu	missense	Exon 4 of 7	ENSP00000229395.3	Q9NVK5-1
	FGFR1OP2	ENST00000546072.5	TSL:1	c.359C>T	p.Pro120Leu	missense	Exon 4 of 5	ENSP00000437556.1	Q9NVK5-3
	FGFR1OP2	ENST00000887799.1		c.359C>T	p.Pro120Leu	missense	Exon 5 of 8	ENSP00000557858.1

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151588 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251066 AF XY: 0.00000737

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461194 Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7 AN XY: 726900

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.0000447 AC: 2 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39612

South Asian (SAS) AF: 0.00 AC: 0 AN: 86198

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

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111638

Other (OTH) AF: 0.0000166 AC: 1 AN: 60356

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151588 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73968

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000485 AC: 2 AN: 41208

American (AMR) AF: 0.0000657 AC: 1 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67944

Other (OTH) AF: 0.00 AC: 0 AN: 2088

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000096912), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

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	0.14
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	T
Eigen	Benign	0.058
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0056	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		5.7
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.22
Sift	Benign	0.17	T
Sift4G	Benign	0.27	T
Polyphen		0.062	B
Vest4		0.81
MVP		0.39
MPC		0.52
ClinPred		0.75	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.35
Mutation Taster		=35/65	disease causing

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

Other links and lift over

dbSNP: rs369150262; hg19: chr12-27110639;