12-26964672-C-T

Variant names:

• chr12-26964672-C-T
• NM_015633.3:c.701C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015633.3(FGFR1OP2):​c.701C>T​(p.Ser234Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,460,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: FGFR1OP2 NM_015633.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.98

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19424298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGFR1OP2	NM_015633.3	c.701C>T	p.Ser234Leu	missense_variant	Exon 7 of 7	ENST00000229395.8	NP_056448.1
FGFR1OP2	NM_001171887.2	c.587C>T	p.Ser196Leu	missense_variant	Exon 6 of 6		NP_001165358.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGFR1OP2	ENST00000229395.8	c.701C>T	p.Ser234Leu	missense_variant	Exon 7 of 7	2	NM_015633.3	ENSP00000229395.3
FGFR1OP2	ENST00000327214.5	c.587C>T	p.Ser196Leu	missense_variant	Exon 6 of 6	2		ENSP00000323763.5
FGFR1OP2	ENST00000538172.1	n.2537C>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460200 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 726418

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.701C>T (p.S234L) alteration is located in exon 7 (coding exon 6) of the FGFR1OP2 gene. This alteration results from a C to T substitution at nucleotide position 701, causing the serine (S) at amino acid position 234 to be replaced by a leucine (L). 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	0.079
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	T;.
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.074
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.099
Sift	Benign	0.24	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.85	P;B
Vest4		0.31
MutPred		0.20		Loss of phosphorylation at S234 (P = 0.0122);.;
MVP		0.36
MPC		0.27
ClinPred		0.63	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.32

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-27117605;