rs11199993

Positions:

• chr10-121531750-G-C

Variant summary

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

The NM_000141.5(FGFR2):​c.748+6842C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0513 in 152,226 control chromosomes in the GnomAD database, including 330 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 0.051 (330 hom., cov: 32)
• Consequence: FGFR2 NM_000141.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.777

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 (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGFR2	NM_000141.5	c.748+6842C>G		intron_variant		ENST00000358487.10
FGFR2	NM_022970.4	c.748+6842C>G		intron_variant		ENST00000457416.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFR2	ENST00000358487.10	c.748+6842C>G		intron_variant		1	NM_000141.5	A2
FGFR2	ENST00000457416.7	c.748+6842C>G		intron_variant		1	NM_022970.4	P4

Frequencies

GnomAD3 genomes AF: 0.0514 AC: 7811 AN: 152108 Hom.: 330 Cov.: 32

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0561

Gnomad ASJ AF: 0.0305

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0491

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0598

Gnomad OTH AF: 0.0608

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

GnomAD4 genome AF: 0.0513 AC: 7809 AN: 152226 Hom.: 330 Cov.: 32 AF XY: 0.0532 AC XY: 3962 AN XY: 74406

Gnomad4 AFR AF: 0.0123

Gnomad4 AMR AF: 0.0559

Gnomad4 ASJ AF: 0.0305

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0491

Gnomad4 NFE AF: 0.0598

Gnomad4 OTH AF: 0.0611

Alfa AF: 0.0535 Hom.: 36

Bravo AF: 0.0499

Asia WGS AF: 0.132 AC: 459 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	7.7
DANN	Benign	0.67

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: rs11199993; hg19: chr10-123291264;