rs2912781

chr10-121576980-C-T

Variant summary

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

The NM_000141.5(FGFR2):c.110-11276G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 148,626 control chromosomes in the GnomAD database, including 14,375 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 0.41 (14375 hom., cov: 24)
• Consequence: FGFR2 NM_000141.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600

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 (NFE) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGFR2	NM_000141.5	c.110-11276G>A		intron_variant		ENST00000358487.10
FGFR2	NM_022970.4	c.110-11276G>A		intron_variant		ENST00000457416.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFR2	ENST00000358487.10	c.110-11276G>A		intron_variant		1	NM_000141.5	A2
FGFR2	ENST00000457416.7	c.110-11276G>A		intron_variant		1	NM_022970.4	P4

Frequencies

GnomAD3 genomes AF: 0.406 AC: 60370 AN: 148514 Hom.: 14362 Cov.: 24

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.406 AC: 60395 AN: 148626 Hom.: 14375 Cov.: 24 AF XY: 0.407 AC XY: 29394 AN XY: 72280

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.449

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.497

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.423

Alfa AF: 0.463 Hom.: 1997

Bravo AF: 0.393

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.2
Dann	Benign	0.45

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: rs2912781; hg19: chr10-123336494;