10-121559447-A-G

Position:

• chr10-121559447-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000141.5(FGFR2):​c.454+5055T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 152,112 control chromosomes in the GnomAD database, including 29,581 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 0.62 (29581 hom., cov: 34)
• Consequence: FGFR2 NM_000141.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63

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]

FGFR2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGFR2	NM_000141.5	c.454+5055T>C		intron_variant		ENST00000358487.10	NP_000132.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGFR2	ENST00000358487.10	c.454+5055T>C		intron_variant		1	NM_000141.5	ENSP00000351276.6
FGFR2	ENST00000457416.7	c.454+5055T>C		intron_variant		1		ENSP00000410294.2
FGFR2	ENST00000369056.5	c.454+5055T>C		intron_variant		1		ENSP00000358052.1
FGFR2	ENST00000369058.7	c.454+5055T>C		intron_variant		1		ENSP00000358054.3
FGFR2	ENST00000613048.4	c.187+5055T>C		intron_variant		5		ENSP00000484154.1
FGFR2	ENST00000369061.8	c.454+5055T>C		intron_variant		1		ENSP00000358057.4
FGFR2	ENST00000369059.5	c.110-7988T>C		intron_variant		5		ENSP00000358055.1
FGFR2	ENST00000360144.7	c.187+5055T>C		intron_variant		2		ENSP00000353262.3
FGFR2	ENST00000604236.5	n.110-7988T>C		intron_variant		1		ENSP00000474109.1

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94048 AN: 151994 Hom.: 29536 Cov.: 34

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.619 AC: 94139 AN: 152112 Hom.: 29581 Cov.: 34 AF XY: 0.618 AC XY: 45942 AN XY: 74350

Gnomad4 AFR AF: 0.720

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.603

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.601

Alfa AF: 0.587 Hom.: 44564

Bravo AF: 0.631

Asia WGS AF: 0.470 AC: 1637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.58

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: rs2912791; hg19: chr10-123318961;