12-26957685-T-C

Position:

• chr12-26957685-T-C

Variant summary

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

The NM_015633.3(FGFR1OP2):​c.338T>C​(p.Met113Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,374 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: FGFR1OP2 NM_015633.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.55

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	UniProt
FGFR1OP2	NM_015633.3	c.338T>C	p.Met113Thr	missense_variant	4/7	ENST00000229395.8
FGFR1OP2	NM_001171887.2	c.338T>C	p.Met113Thr	missense_variant	4/6
FGFR1OP2	NM_001171888.2	c.338T>C	p.Met113Thr	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFR1OP2	ENST00000229395.8	c.338T>C	p.Met113Thr	missense_variant	4/7	2	NM_015633.3
FGFR1OP2	ENST00000546072.5	c.338T>C	p.Met113Thr	missense_variant	4/5	1
FGFR1OP2	ENST00000327214.5	c.338T>C	p.Met113Thr	missense_variant	4/6	2		P1
FGFR1OP2	ENST00000395941.4	n.579T>C		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000199 AC: 5 AN: 251212 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135778

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1461374 Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11 AN XY: 727008

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000429

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Pathogenic	0.26
CADD	Uncertain	23
DANN	Uncertain	0.97
DEOGEN2	Benign	0.046	T;.;.
Eigen	Benign	0.087
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.80	T;T;D
M_CAP	Benign	0.0069	T
MetaRNN	Uncertain	0.53	D;D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.4	M;M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.3	N;N;N
REVEL	Uncertain	0.47
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.61	T;T;T
Polyphen		0.41	B;B;B
Vest4		0.91
MutPred		0.45		Gain of phosphorylation at M113 (P = 0.0203);Gain of phosphorylation at M113 (P = 0.0203);Gain of phosphorylation at M113 (P = 0.0203);
MVP		0.35
MPC		0.80
ClinPred		0.34	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.40

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

LitVar

Other links and lift over

dbSNP: rs367585257; hg19: chr12-27110618;