rs2046937

chr12-26956722-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015633.3(FGFR1OP2):c.253+62A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0614 in 951,194 control chromosomes in the GnomAD database, including 2,561 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.083 (774 hom., cov: 31)
  • Exomes 𝑓: 0.057 (1787 hom.)
• Consequence: FGFR1OP2 NM_015633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.692

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGFR1OP2	NM_015633.3	c.253+62A>G		intron_variant		ENST00000229395.8
FGFR1OP2	NM_001171887.2	c.253+62A>G		intron_variant
FGFR1OP2	NM_001171888.2	c.253+62A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFR1OP2	ENST00000229395.8	c.253+62A>G		intron_variant		2	NM_015633.3
FGFR1OP2	ENST00000546072.5	c.253+62A>G		intron_variant		1
FGFR1OP2	ENST00000327214.5	c.253+62A>G		intron_variant		2		P1
FGFR1OP2	ENST00000395941.4	n.494+62A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0825 AC: 12535 AN: 152008 Hom.: 769 Cov.: 31

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0527

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0691

Gnomad FIN AF: 0.0302

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.0505

Gnomad OTH AF: 0.0812

GnomAD4 exome AF: 0.0574 AC: 45874 AN: 799068 Hom.: 1787 AF XY: 0.0585 AC XY: 24443 AN XY: 417534

Gnomad4 AFR exome AF: 0.186

Gnomad4 AMR exome AF: 0.0356

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.000180

Gnomad4 SAS exome AF: 0.0878

Gnomad4 FIN exome AF: 0.0314

Gnomad4 NFE exome AF: 0.0519

Gnomad4 OTH exome AF: 0.0716

GnomAD4 genome AF: 0.0826 AC: 12564 AN: 152126 Hom.: 774 Cov.: 31 AF XY: 0.0816 AC XY: 6068 AN XY: 74370

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.0526

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0700

Gnomad4 FIN AF: 0.0302

Gnomad4 NFE AF: 0.0505

Gnomad4 OTH AF: 0.0799

Alfa AF: 0.0702 Hom.: 181

Bravo AF: 0.0893

Asia WGS AF: 0.0450 AC: 157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	6.6
Dann	Benign	0.53

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: rs2046937; hg19: chr12-27109655;