rs2912795

Positions:

• chr10-121490734-G-A
• chr10-121490734-G-C
• chr10-121490734-G-T

Variant summary

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

The NM_000141.5(FGFR2):​c.1864-2621C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 151,920 control chromosomes in the GnomAD database, including 18,173 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 0.46 (18173 hom., cov: 32)
• Consequence: FGFR2 NM_000141.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGFR2	NM_000141.5	c.1864-2621C>T		intron_variant		ENST00000358487.10
FGFR2	NM_022970.4	c.1867-2621C>T		intron_variant		ENST00000457416.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFR2	ENST00000358487.10	c.1864-2621C>T		intron_variant		1	NM_000141.5	A2
FGFR2	ENST00000457416.7	c.1867-2621C>T		intron_variant		1	NM_022970.4	P4

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69742 AN: 151802 Hom.: 18159 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.459 AC: 69782 AN: 151920 Hom.: 18173 Cov.: 32 AF XY: 0.461 AC XY: 34253 AN XY: 74268

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.485

Alfa AF: 0.525 Hom.: 5248

Bravo AF: 0.459

Asia WGS AF: 0.464 AC: 1613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.73
DANN	Benign	0.59

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: rs2912795; hg19: chr10-123250248;