rs4752571

Positions:

• chr10-121583053-T-C

Variant summary

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

The NM_000141.5(FGFR2):​c.109+10656A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,056 control chromosomes in the GnomAD database, including 10,982 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 0.38 (10982 hom., cov: 32)
• Consequence: FGFR2 NM_000141.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.632

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGFR2	NM_000141.5	c.109+10656A>G		intron_variant		ENST00000358487.10	NP_000132.3
FGFR2	NM_022970.4	c.109+10656A>G		intron_variant		ENST00000457416.7	NP_075259.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGFR2	ENST00000358487.10	c.109+10656A>G		intron_variant		1	NM_000141.5	ENSP00000351276	A2
FGFR2	ENST00000457416.7	c.109+10656A>G		intron_variant		1	NM_022970.4	ENSP00000410294	P4

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57436 AN: 151940 Hom.: 10976 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.385

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.378 AC: 57456 AN: 152056 Hom.: 10982 Cov.: 32 AF XY: 0.381 AC XY: 28352 AN XY: 74324

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.381

Alfa AF: 0.380 Hom.: 3390

Bravo AF: 0.374

Asia WGS AF: 0.348 AC: 1215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	12
DANN	Benign	0.71

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: rs4752571; hg19: chr10-123342567;