rs1939131785

Variant names:

• chr12-26963406-T-C
• rs1939131785
• NM_015633.3:c.575T>C

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.575T>C​(p.Ile192Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FGFR1OP2 NM_015633.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.28
• 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=0.26312503).

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.575T>C	p.Ile192Thr	missense	Exon 6 of 7	NP_056448.1	Q9NVK5-1
	FGFR1OP2	NM_001171887.2		c.461T>C	p.Ile154Thr	missense	Exon 5 of 6	NP_001165358.1	Q9NVK5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGFR1OP2	ENST00000229395.8	TSL:2 MANE Select	c.575T>C	p.Ile192Thr	missense	Exon 6 of 7	ENSP00000229395.3	Q9NVK5-1
	FGFR1OP2	ENST00000887799.1		c.575T>C	p.Ile192Thr	missense	Exon 7 of 8	ENSP00000557858.1
	FGFR1OP2	ENST00000887801.1		c.575T>C	p.Ile192Thr	missense	Exon 6 of 7	ENSP00000557860.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456742 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724894

African (AFR) AF: 0.00 AC: 0 AN: 33296

American (AMR) AF: 0.00 AC: 0 AN: 44242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25954

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39460

South Asian (SAS) AF: 0.00 AC: 0 AN: 85692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108994

Other (OTH) AF: 0.00 AC: 0 AN: 60100

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.11
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.6	L
PhyloP100		7.3
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.030	D
Polyphen		0.60	P
Vest4		0.49
MutPred		0.37		Loss of stability (P = 0.0103)
MVP		0.47
MPC		0.41
ClinPred		0.96	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.44
gMVP		0.35
Mutation Taster		=67/33	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: rs1939131785; hg19: chr12-27116339;