rs1801043

chr10-121538071-C-T

Variant summary

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

The ENST00000359354.6(FGFR2):c.*323G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0743 in 483,658 control chromosomes in the GnomAD database, including 1,733 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 0.067 (491 hom., cov: 33)
  • Exomes 𝑓: 0.078 (1242 hom.)
• Consequence: FGFR2 ENST00000359354.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.911

Genes affected

FGFR2 (HGNC:3689): (fibroblast growth factor receptor 2) The protein encoded by this gene is a member of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member is a high-affinity receptor for acidic, basic and/or keratinocyte growth factor, depending on the isoform. Mutations in this gene are associated with Crouzon syndrome, Pfeiffer syndrome, Craniosynostosis, Apert syndrome, Jackson-Weiss syndrome, Beare-Stevenson cutis gyrata syndrome, Saethre-Chotzen syndrome, and syndromic craniosynostosis. Multiple alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGFR2	NM_000141.5	c.748+521G>A		intron_variant		ENST00000358487.10
FGFR2	NM_022970.4	c.748+521G>A		intron_variant		ENST00000457416.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFR2	ENST00000358487.10	c.748+521G>A		intron_variant		1	NM_000141.5	A2
FGFR2	ENST00000457416.7	c.748+521G>A		intron_variant		1	NM_022970.4	P4

Frequencies

GnomAD3 genomes AF: 0.0670 AC: 10189 AN: 152098 Hom.: 490 Cov.: 33

Gnomad AFR AF: 0.0154

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0930

Gnomad ASJ AF: 0.0712

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0358

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0929

Gnomad OTH AF: 0.0764

GnomAD4 exome AF: 0.0777 AC: 25754 AN: 331442 Hom.: 1242 Cov.: 0 AF XY: 0.0757 AC XY: 13085 AN XY: 172908

Gnomad4 AFR exome AF: 0.0156

Gnomad4 AMR exome AF: 0.0973

Gnomad4 ASJ exome AF: 0.0798

Gnomad4 EAS exome AF: 0.000175

Gnomad4 SAS exome AF: 0.0417

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.0920

Gnomad4 OTH exome AF: 0.0726

GnomAD4 genome AF: 0.0669 AC: 10189 AN: 152216 Hom.: 491 Cov.: 33 AF XY: 0.0677 AC XY: 5041 AN XY: 74406

Gnomad4 AFR AF: 0.0153

Gnomad4 AMR AF: 0.0932

Gnomad4 ASJ AF: 0.0712

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0359

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.0928

Gnomad4 OTH AF: 0.0756

Alfa AF: 0.0896 Hom.: 171

Bravo AF: 0.0638

Asia WGS AF: 0.0230 AC: 79 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.5
Dann	Benign	0.38

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: rs1801043; hg19: chr10-123297585;