rs7073360

Positions:

• chr10-121548220-T-G

Variant summary

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

The NM_000141.5(FGFR2):​c.624+3070A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0787 in 139,976 control chromosomes in the GnomAD database, including 1,118 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 0.079 (1118 hom., cov: 29)
• Consequence: FGFR2 NM_000141.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGFR2	NM_000141.5	c.624+3070A>C		intron_variant		ENST00000358487.10
FGFR2	NM_022970.4	c.624+3070A>C		intron_variant		ENST00000457416.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFR2	ENST00000358487.10	c.624+3070A>C		intron_variant		1	NM_000141.5	A2
FGFR2	ENST00000457416.7	c.624+3070A>C		intron_variant		1	NM_022970.4	P4

Frequencies

GnomAD3 genomes AF: 0.0784 AC: 10967 AN: 139904 Hom.: 1105 Cov.: 29

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.0423

Gnomad AMR AF: 0.0781

Gnomad ASJ AF: 0.00476

Gnomad EAS AF: 0.0817

Gnomad SAS AF: 0.00756

Gnomad FIN AF: 0.0330

Gnomad MID AF: 0.00360

Gnomad NFE AF: 0.00228

Gnomad OTH AF: 0.0584

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

GnomAD4 genome AF: 0.0787 AC: 11019 AN: 139976 Hom.: 1118 Cov.: 29 AF XY: 0.0802 AC XY: 5380 AN XY: 67108

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.0790

Gnomad4 ASJ AF: 0.00476

Gnomad4 EAS AF: 0.0808

Gnomad4 SAS AF: 0.00782

Gnomad4 FIN AF: 0.0330

Gnomad4 NFE AF: 0.00228

Gnomad4 OTH AF: 0.0586

Alfa AF: 0.0549 Hom.: 110

Bravo AF: 0.0898

Asia WGS AF: 0.0510 AC: 177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.50

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: rs7073360; hg19: chr10-123307734; COSMIC: COSV60645485;