rs35054928

chr10-121580917-GC-Gchr10-121580917-GC-GCC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000141.5(FGFR2):c.109+12791del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.53 (21759 hom., cov: 0)
• Consequence: FGFR2 NM_000141.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

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 -10 ACMG points.

• BP6: Variant 10-121580917-GC-G is Benign according to our data. Variant chr10-121580917-GC-G is described in ClinVar as [Benign]. Clinvar id is 1659816.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGFR2	NM_000141.5	c.109+12791del		intron_variant		ENST00000358487.10
FGFR2	NM_022970.4	c.109+12791del		intron_variant		ENST00000457416.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFR2	ENST00000358487.10	c.109+12791del		intron_variant		1	NM_000141.5	A2
FGFR2	ENST00000457416.7	c.109+12791del		intron_variant		1	NM_022970.4	P4

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80129 AN: 151834 Hom.: 21732 Cov.: 0

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.528 AC: 80192 AN: 151954 Hom.: 21759 Cov.: 0 AF XY: 0.526 AC XY: 39067 AN XY: 74254

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.551

Gnomad4 SAS AF: 0.603

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.553

Alfa AF: 0.574 Hom.: 3092

Bravo AF: 0.520

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

FGFR2-related craniosynostosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

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Computational scores

Source: dbNSFP v4.3

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: rs35054928; hg19: chr10-123340431;