chr12-26956722-A-G

Variant names:

• chr12-26956722-A-G
• rs2046937
• NM_015633.3:c.253+62A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
FGFR1OP2	NM_015633.3	c.253+62A>G		intron_variant	Intron 3 of 6	ENST00000229395.8	NP_056448.1
FGFR1OP2	NM_001171887.2	c.253+62A>G		intron_variant	Intron 3 of 5		NP_001165358.1
FGFR1OP2	NM_001171888.2	c.253+62A>G		intron_variant	Intron 3 of 4		NP_001165359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGFR1OP2	ENST00000229395.8	c.253+62A>G		intron_variant	Intron 3 of 6	2	NM_015633.3	ENSP00000229395.3

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

African (AFR) AF: 0.186 AC: 3428 AN: 18416

American (AMR) AF: 0.0356 AC: 1069 AN: 30010

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 2421 AN: 16870

East Asian (EAS) AF: 0.000180 AC: 5 AN: 27816

South Asian (SAS) AF: 0.0878 AC: 5358 AN: 61016

European-Finnish (FIN) AF: 0.0314 AC: 1334 AN: 42520

Middle Eastern (MID) AF: 0.150 AC: 456 AN: 3044

European-Non Finnish (NFE) AF: 0.0519 AC: 29355 AN: 565166

Other (OTH) AF: 0.0716 AC: 2448 AN: 34210

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

African (AFR) AF: 0.168 AC: 6975 AN: 41472

American (AMR) AF: 0.0526 AC: 805 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 460 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.0700 AC: 338 AN: 4828

European-Finnish (FIN) AF: 0.0302 AC: 319 AN: 10580

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.0505 AC: 3433 AN: 67984

Other (OTH) AF: 0.0799 AC: 169 AN: 2116

Alfa AF: 0.0696 Hom.: 274

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
PhyloP100		0.69
Mutation Taster		=100/0	polymorphism (auto)

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: rs2046937; hg19: chr12-27109655;